Critical windows of perinatal particulate matter (PM2.5) exposure and preadolescent kidney function.

Air pollution exposure, especially particulate matter ≤2.5 µm in diameter (PM2.5), is associated with poorer kidney function in adults and children. Perinatal exposure may occur during susceptible periods of nephron development. We used distributed lag nonlinear models (DLNMs) to examine time-varying associations between early life daily PM2.5 exposure (periconceptional through age 8 years) and kidney parameters in preadolescent children aged 8-10 years. Participants included 427 mother-child dyads enrolled in the PROGRESS birth cohort study based in Mexico City. Daily PM2.5 exposure was estimated at each participant's residence using a validated satellite-based spatio-temporal model. Kidney function parameters included estimated glomerular filtration rate (eGFR), serum cystatin C, and blood urea nitrogen (BUN). Models were adjusted for child's age, sex and body mass index (BMI) z-score, as well as maternal education, indoor smoking report and seasonality (prenatal models were additionally adjusted for average first year of life PM2.5 exposure). We also tested for sex-specific effects. Average perinatal PM2.5 was 22.7 µg/m3 and ranged 16.4-29.3 µg/m3. Early pregnancy PM2.5 exposures were associated with higher eGFR in preadolescence. Specifically, we found that PM2.5 exposure between weeks 1-18 of gestation was associated with increased preadolescent eGFR, whereas exposure in the first 14 months of life after birth were associated with decreased eGFR. Specifically, a 5 µg/m3 increase in PM2.5 during the detected prenatal window was associated with a cumulative increase in eGFR of 4.44 mL/min/1.732 (95%CI: 1.37, 7.52), and during the postnatal window we report a cumulative eGFR decrease of -10.36 mL/min/1.732 (95%CI: -17.68, -3.04). We identified perinatal windows of susceptibility to PM2.5 exposure with preadolescent kidney function parameters. Follow-up investigating PM2.5 exposure with peripubertal kidney function trajectories and risk of kidney disease in adulthood will be critical.

In utero and peripubertal metals exposure in relation to reproductive hormones and sexual maturation and progression among boys in Mexico City.

BACKGROUND: Endocrine disrupting chemicals (EDCs) such as metals have been reported to alter circulating reproductive hormone concentrations and pubertal development in animals. However, the relationship has rarely been investigated among humans, with the exception of heavy metals, such as Pb and Cd. Our aim was to investigate measures of in utero and peripubertal metal exposure in relation to reproductive hormone concentrations and sexual maturation and progression among boys from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohorts. METHODS: Our analysis included 118 pregnant women and their male children from the ELEMENT study. Essential and non-essential metals were measured in urine collected from the mothers during the third trimester of pregnancy and their male children at 8-14 years. Reproductive hormone concentrations [serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG)] were measured in blood samples from the children at 8-14 years. We also assessed Tanner stages for sexual maturation (genital, pubic hair development, and testicular volume), at two time points (8-14, 10-18 years). We used linear regression to independently examine urinary metal concentrations in relation to each peripubertal reproductive hormones adjusting for child age and BMI. Generalized estimation equations (GEEs) were used to evaluate the association of in utero and peripubertal metal exposures with sexual maturation and progression during follow-up based on Tanner staging and testicular volume. RESULTS: In utero and prepubertal concentrations of some urinary metals were associated with increased concentrations of peripubertal reproductive hormones, especially non-essential metal(loid)s As and Cd (in utero), and Ba (peripubertal) as well as essential metal Mo (in utero) in association with testosterone. More advanced pubic hair developmental stage and higher testicular volume at the early teen visit was observed for boys with higher non-essential metal concentrations, including in utero Al and peripubertal Ba, and essential metal Zn concentration (peripubertal). These metals were also associated with slower pubertal progression between the two visits. CONCLUSION: These findings suggest that male reproductive development may be associated with both essential and non-essential metal exposure during in utero and peripubertal windows.

Dietary Patterns Exhibit Sex-Specific Associations with Adiposity and Metabolic Risk in a Cross-Sectional Study in Urban Mexican Adolescents.

Background: Studies in Western nations have shown associations of certain dietary patterns with obesity and metabolic risk in youth. Little is known about these relations in newly industrialized countries where obesity prevalence is surpassing those of developed countries.Objective: We sought to characterize dietary patterns in a cross-sectional study in 224 adolescents aged 8-14 y in Mexico and to investigate associations of the dietary patterns with adiposity and metabolic risk.Methods: We used principal components analysis to derive dietary patterns from food-frequency questionnaire data. By using linear regression models that accounted for mother's marital status, education, and smoking habits and child's age and physical activity, we examined associations of the dietary patterns with adiposity [body mass index z score, waist circumference, the sum and ratio of the subscapular and triceps skinfold thicknesses, blood pressure, serum fasting glucose and a C-peptide-based measure of insulin resistance (CP-IR), lipid profile, and a metabolic syndrome risk z score (MetS z score)].Results: We identified a "prudent" dietary pattern characterized by high intakes of vegetables, fruit, fish, chicken, and legumes and a "transitioning" dietary pattern, which comprises processed meats, Mexican foods, and sweetened beverages. Each unit increase in the prudent pattern factor score corresponded with 0.33 ng/mL (95% CI: 0.09, 0.57 ng/mL) lower C-peptide, 0.08 units (95% CI: 0.02, 0.13 units) lower CP-IR, and a 0.14 unit (0.00, 0.27 unit) lower MetS z score in boys. In girls, the transitioning pattern corresponded with higher subscapular + triceps skinfold thickness (per 1-unit increase in the factor score: 2.46 mm; 95% CI: 0.10, 4.81 mm). These results did not change after accounting for pubertal status.Conclusions: A prudent dietary pattern was protective against metabolic risk in adolescent boys, whereas a transitioning dietary pattern corresponded with higher adiposity among adolescent girls. Given that adolescence is a key developmental period for long-term health, efforts to elucidate dietary determinants of metabolic risk during this life stage may have long-term benefits.

Dietary predictors of urinary cadmium among pregnant women and children.

BACKGROUND: Cadmium is a toxic metal with modifiable exposure sources including diet. In pregnant women and children, unique dietary habits may contribute to DCd, and the relationship of diet to overall cadmium exposure can depend on specific factors during these transitional time periods. OBJECTIVES: This study aimed to identify and quantify food sources of DCd, describe the distribution of UCd, and determine the relationship of DCd and intake of specific foods with UCd, stratified by maternal smoking history, among pregnant women and children in a well-characterized Mexico City birth cohort. METHODS: Our sample included 192 pregnant women (third trimester) and 223 children (7-15years). DCd was calculated using FFQ and the U.S. TDS. We also measured UCd, maternal history of smoking, and additional covariates. RESULTS: Pregnant women and children had geometric mean UCd concentrations of 0.19±0.78µg/L and 0.14±0.60µg/L, respectively. On average, estimated daily DCd intake was 9.3±3.5µg for women and 12.2±5.4µg for children. Adjusted linear regression models showed a positive association between DCd and UCd among women (p=0.03) and children (p=0.03) without a maternal history of smoking. Intake of fruit and vegetables among women and potato consumption among children were positively associated with UCd. CONCLUSIONS: Pregnant women and their children are exposed to cadmium at dietary and urinary levels similar to those previously reported. Higher estimated DCd for children than for women could be attributed to the different FFQs or related to dietary pattern changes between age groups. DCd contributed to UCd in those without a maternal smoking history.

Offspring DNA methylation of the aryl-hydrocarbon receptor repressor gene is associated with maternal BMI, gestational age, and birth weight.

Prenatal smoke exposure, maternal obesity, aberrant fetal growth, and preterm birth are all risk factors for offspring metabolic syndrome. Cord blood aryl-hydrocarbon receptor repressor (AHRR) DNA methylation is responsive to maternal smoking during pregnancy. AHRR serves not only to inhibit aryl-hydrocarbon receptor (AHR) transcription, which is involved in mediating xenobiotic metabolism, but it is also involved in cell growth and differentiation. Other than maternal smoking, other predictors of offspring AHRR DNA methylation status remain unknown; we sought to identify them among newborns. We enrolled pregnant women in the PROGRESS birth cohort in Mexico City. Using pyrosequencing, we analyzed DNA methylation of 3 CpG sites within the AHRR gene promoter from the umbilical cord blood of 531 infants. We used generalized estimating equations to account for the correlation of DNA methylation between CpG sites. Multivariable models were used to adjust for maternal age, BMI, education, parity, smoke-exposure, infant sex, gestational age, and birth weight-for-gestational age. AHRR DNA methylation was positively associated with maternal BMI (P = 0.0009) and negatively associated with the length of gestation (P < 0.0001) and birth weight-for-gestational age (P < 0.0001). AHRR DNA methylation was 2.1% higher in offspring of obese vs. normal weight mothers and 3.1% higher in preterm vs. term infants, representing a third and a half standard deviation differences in methylation, respectively. In conclusion, offspring AHRR DNA methylation was associated with maternal obesity during pregnancy as well as infant gestational age and birth weight-for-gestational age. Further work to discover the health impacts of altered AHRR DNA methylation is warranted.

Consumo de alimentos y asma en niños escolares de Cuernavaca / Food consumption and asthma in school children in Cuernavaca, Morelos, Mexico

OBJETIVO:Evaluar la relación entre la dieta y el desarrollo de asma y rinitis alérgica en escolares de Cuernavaca, Morelos, México. MATERIAL Y MÉTODOS: Se aplicó el cuestionario ISAAC (International Study of Asthma and Allergies in Childhood) a 5 460 niños de entre 6 a 8 y 11 a 14 años de edad, de nivel primaria, seleccionados de manera aleatoria. Se formaron seis grupos de alimentos a partir de un análisis de clusters jerárquico y se evaluó la relación con los padecimientos a través de modelos de regresión logística. RESULTADOS:El consumo de comida rápida tuvo un efecto adverso sobre la sibilancia actual (RM=1.82; IC95%=1.16-2.87) y el consumo de golosinas sobre más de tres episodios de sibilancia (RM=2.26; IC95%=1.04-4.95) y síntomas nasales sin gripa o catarro (RM=1.35; IC95%=1.06-1.71). CONCLUSIONES:Este estudio provee evidencia de que la dieta juega un papel muy importante, ya que el consumo abundante de comida rápida y golosinas incrementa el riesgo de asma y rinitis.

OBJECTIVE:To evaluate the relation between diet and the development of asthma and allergic rhinitis in schoolchildren from Cuernavaca, Morelos, Mexico. MATERIAL AND METHODS:We apply the ISAAC's questionnaire in 5460 schoolchildren from 6 to 8 and 11-14-year-old of elementary level selected in random form. Six groups of food were formed using a hierarchic clusters analysis and the association was evaluated using logistic regression models. RESULTS:The consumption of fast food had an adverse effect for current wheezing (OR=1.82; CI95%=1.16-2.87) and the consumption of tidbits for more than three episodes of wheezing (OR=2.26; CI95%=1.04-4.95) and nasal symptoms without cold, OR=1.35 (IC95%;1.06-1.71). CONCLUSIONS:This study provides evidence that the diet plays a very important role since the high consumption of fast food and tidbits increased the risk of asthma and rhinitis symptoms.

High dietary calcium intake decreases bone mobilization during pregnancy in humans.

UNLABELLED: Calcium metabolism of the mother is modified during pregnancy because of the mineralization of the fetus skeleton. OBJECTIVE: To evaluate the association of calcium intake and bone demineralization during pregnancy. MATERIAL AND METHODS: At each trimester of pregnancy a validated food frequency intake questionnaire was administered to assess individual daily calcium intake in a cohort of 206 pregnant women, residents of Mexico City. Samples of urine were collected to measure levels of the cross-linked N-telopeptide of type I collagen (NTx), which is a biomarker of bone resorption. The association between calcium ingestion and bone resorption was analyzed using random effects models; non-linear associations were explored using generalized additive models. RESULTS: Progressive increases in NTx levels were observed during pregnancy; with mean and standard deviation (SD) values during the first, second and third trimester of 76.50 (SD=38), 101.02 (SD=48.86) and 144.83 (SD=61.33) nmol BCE/mmol creatinine, respectively. Higher dietary calcium intake was associated with lower bone resorption (beta=-0.015; p<0.05). The association between age and NTx showed a non-linear trend with an inflexion point around 33 years: increase in maternal age below that point was associated with a decrease in bone resorption, while in older women the increase in age was associated with an increased resorption. CONCLUSIONS: Our results suggest that calcium ingestion, specifically from dairy products, reduces bone resorption during pregnancy. For each 300 mg (a glass of milk) of calcium intake there is an estimated reduction in NTx level of 4.8 nmol BCE/mmol of creatinine (p<0.05).

High dietary calcium intake decreases bone mobilization during pregnancy in humans / Alto consumo de calcio en la dieta, disminuye la movilización ósea durante el embarazo en seres humanos

Calcium metabolism of the mother is modified during pregnancy because of the mineralization of the fetus skeleton. OBJECTIVE: To evaluate the association of calcium intake and bone demineralization during pregnancy. MATERIAL AND METHODS: At each trimester of pregnancy a validated food frequency intake questionnaire was administered to assess individual daily calcium intake in a cohort of 206 pregnant women, residents of Mexico City. Samples of urine were collected to measure levels of the cross-linked N-telopeptide of type I collagen (NTx), which is a biomarker of bone resorption. The association between calcium ingestion and bone resorption was analyzed using random effects models; non-linear associations were explored using generalized additive models. RESULTS: Progressive increases in NTx levels were observed during pregnancy; with mean and standard deviation (SD) values during the first, second and third trimester of 76.50 (SD=38), 101.02 (SD=48.86) and 144.83 (SD=61.33) nmol BCE/mmol creatinine, respectively. Higher dietary calcium intake was associated with lower bone resorption (β=-0.015; p<0.05). The association between age and NTx showed a non-linear trend with an inflexion point around 33 years: increase in maternal age below that point was associated with a decrease in bone resorption, while in older women the increase in age was associated with an increased resorption. CONCLUSIONS: Our results suggest that calcium ingestion, specifically from dairy products, reduces bone resorption during pregnancy. For each 300mg (a glass of milk) of calcium intake there is an estimated reduction in NTx level of 4.8 nmol BCE/mmol of creatinine (p<0.05).

El metabolismo de calcio es modificado durante el embarazo debido a la mineralización del esqueleto del feto. OBJETIVO: Evaluar la asociación entre la ingesta de calcio y la desmineralización ósea durante el embarazo. MATERIAL Y MÉTODOS: Se administró un Cuestionario de Frecuencia de Consumo de alimentos en cada trimestre del embarazo para evaluar el consumo de calcio en una cohorte de 206 mujeres residentes de la Ciudad de México. Se recolectaron muestras de orina para medir los niveles de N-telopéptido de colágeno tipo I (NTx), biomarcador de resorción. Se hicieron modelos de efectos aleatorios; se estudiaron asociaciones no lineales utilizando modelos aditivos generalizados. RESULTADOS: Se observó aumento progresivo en los niveles de NTx durante el embarazo. El mayor consumo de calcio se asoció con una menor resorción ósea (β=- 0.015, p<0,05). CONCLUSIONES: Los resultados sugieren que la ingestión de calcio reduce la resorción ósea en el embarazo.

Exposición al plomo y su relación con el tiempo requerido para embarazo / Lead exposure and time to pregnancy

OBJETIVO: Determinar los efectos de la exposición al plomo relacionados con el tiempo requerido para embarazo. MATERIAL Y MÉTODOS: Entre 1997 y 2001 se realizó un estudio en 142 mujeres residentes en la Ciudad de México, participantes en un estudio de cohorte para evaluar diversos efectos del plomo sobre la salud reproductiva. Se realizaron mediciones de plomo en sangre y en hueso a cada una de las participantes en el momento de ingresar al estudio, y se obtuvo información relativa a la exposición y otras variables de interés a través de un cuestionario. A cada una de las participantes se les siguió hasta el momento en que se embarazaron, o bien, hasta el tiempo de término del estudio, con el propósito de determinar la asociación entre la exposición al plomo y el tiempo requerido para quedar embarazada. El análisis estadístico se llevó a cabo utilizando curvas de Kaplan-Meier y modelos de riesgos proporcionales de Cox. RESULTADOS: Del total de mujeres que iniciaron el estudio se embarazaron 42, de las cuales 34 lo lograron antes del primer año de seguimiento y ocho posteriormente. Las medias de las concentraciones de plomo en sangre fueron de 9.3 æg/dl; en rótula y tibia fueron de 16.0 y 11.0 æg Pb/g de hueso mineral, respectivamente. No se detectaron diferencias en los niveles de plomo en sangre respecto al tiempo que durante el estudio requirió la mujer para embarazarse en el primer año; no obstante, se encontró que en las mujeres con plomo en sangre por encima de 10 æg/dl el riesgo de no embarazo fue cinco veces mayor [IC 95 por ciento (1.9-19.1)] después de un año de seguimiento, comparado con aquellas mujeres con plomo en sangre por debajo de 10 æg/dl. CONCLUSIONES: La exposición a concentraciones altas de plomo puede ser un factor de riesgo importante en el tiempo requerido para que una mujer quede embarazada, principalmente en aquellas que siendo fértiles tienen periodos mayores de un año buscando un embarazo.