Calcium supplementation and body mass index modify associations between prenatal phthalate exposure and perinatal bone ultrasound measures among pregnant women.

Phthalates have endocrine activity that may interfere with bone health, particularly during pregnancy and the early postpartum period, when bone resorption increases. We evaluated associations between prenatal phthalate exposure and perinatal bone health among 289 mothers in the ELEMENT birth cohort in Mexico City who were randomized upon recruitment to receive 1,200 mg daily calcium supplementation or placebo throughout pregnancy. Spot urine samples at up to three timepoints during pregnancy were assayed for 9 phthalate metabolites. Bone integrity was assessed by quantitative ultrasound speed of sound (SOS) measurements of the phalange and distal radius at 3, 6, and 8 months of pregnancy and 1, 3, 7, and 12 months postpartum. Geometric means of specific gravity-corrected phthalate concentrations were used as overall measures of prenatal exposure. Linear mixed effect models estimated associations between phthalate exposure and repeated perinatal bone SOS measures, adjusting for age, pre-pregnancy body mass index (BMI), education, parity, calcium supplementation, and month of pregnancy/postpartum. Effect modification by calcium supplementation and BMI were assessed in sensitivity analyses. An interquartile range increase in MEP and MiBP increased pregnancy phalange z-scores (ß: 0.11; 95%CI: 0.003, 0.31 and ß: 0.15; 95%CI: 0.00,0.42, respectively). Higher concentrations of several phthalate metabolites resulted in lower SOS measures among women who received calcium supplements (compared to placebo group) but higher SOS measures among women with a BMI≥25 (compared to BMI<25). These results suggest that phthalate exposure may interfere with bone remodeling during pregnancy, and that consideration of effect modifiers is paramount to fully understand the effects of environmental exposures on bone health.

Plasma DHA Is Related to Sleep Timing and Duration in a Cohort of Mexican Adolescents.

BACKGROUND: Delayed sleep timing and short sleep duration represent a significant public health burden in adolescents. Whether intake of nutrients affects the pineal gland, where sleep/wake cycles are regulated, remains unclear. OBJECTIVES: In a cross-sectional analysis, we investigated whether plasma concentrations of DHA and arachidonic acid (AA), long-chain fatty acids that can be obtained through diet, were related to sleep timing and duration in adolescents. METHODS: The study population included 405 Mexico City adolescents (mean age ± SD = 14.2 ± 2.1 y; 48% males) who took part in a 2015-2016 follow-up visit as a part of an ongoing cohort study. Fatty acid concentrations were measured in plasma using GLC, as a percentage of total fatty acids. Sleep midpoint and duration were assessed with 7-d wrist actigraphy. We categorized DHA and AA plasma concentrations into quartiles (Q1-Q4; Q4 = highest fatty acids). We conducted cross-sectional linear regression analysis with sleep characteristics as separate outcomes and quartiles of DHA and AA as exposures, adjusting for sex, age, and BMI z-scores. RESULTS: Mean ± SD plasma DHA (as percentage of total fatty acids) was 1.2 ± 0.4%, whereas mean ± SD plasma AA was 6.2 ± 1.5%. In adjusted analysis, higher plasma DHA was linearly associated with longer sleep duration on the weekends; to illustrate, those in Q4 compared with Q1 had 32 min longer duration (95% CI: 7, 57; P trend = 0.005). Higher DHA was also associated with earlier sleep timing during weekdays and weekends, although in a nonlinear fashion. The largest difference was a 0.75-h (45-min) later sleep midpoint in Q2 compared with Q4 (95% CI: 0.36, 1.14). CONCLUSIONS: Plasma DHA was associated with earlier sleep timing and longer weekend sleep duration in Mexican adolescents. Whether DHA supplementation improves sleep in adolescent populations deserves consideration in randomized trials.

Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) Project.

PURPOSE: The Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) Project is a mother-child pregnancy and birth cohort originally initiated in the mid-1990s to explore: (1) whether enhanced mobilisation of lead from maternal bone stores during pregnancy poses a risk to fetal and subsequent offspring neurodevelopment; and (2) whether maternal calcium supplementation during pregnancy and lactation can suppress bone lead mobilisation and mitigate the adverse effects of lead exposure on offspring health and development. Through utilisation of carefully archived biospecimens to measure other prenatal exposures, banking of DNA and rigorous measurement of a diverse array of outcomes, ELEMENT has since evolved into a major resource for research on early life exposures and developmental outcomes. PARTICIPANTS: n=1643 mother-child pairs sequentially recruited (between 1994 and 2003) during pregnancy or at delivery from maternity hospitals in Mexico City, Mexico. FINDINGS TO DATE: Maternal bone (eg, patella, tibia) is an endogenous source for fetal lead exposure due to mobilisation of stored lead into circulation during pregnancy and lactation, leading to increased risk of miscarriage, low birth weight and smaller head circumference, and transfer of lead into breastmilk. Daily supplementation with 1200 mg of elemental calcium during pregnancy and lactation reduces lead resorption from maternal bone and thereby, levels of circulating lead. Beyond perinatal outcomes, early life exposure to lead is associated with neurocognitive deficits, behavioural disorders, higher blood pressure and lower weight in offspring during childhood. Some of these relationships were modified by dietary factors; genetic polymorphisms specific for iron, folate and lipid metabolism; and timing of exposure. Research has also expanded to include findings published on other toxicants such as those associated with personal care products and plastics (eg, phthalates, bisphenol A), other metals (eg, mercury, manganese, cadmium), pesticides (organophosphates) and fluoride; other biomarkers (eg, toxicant levels in plasma, hair and teeth); other outcomes (eg, sexual maturation, metabolic syndrome, dental caries); and identification of novel mechanisms via epigenetic and metabolomics profiling. FUTURE PLANS: As the ELEMENT mothers and children age, we plan to (1) continue studying the long-term consequences of toxicant exposure during the perinatal period on adolescent and young adult outcomes as well as outcomes related to the original ELEMENT mothers, such as their metabolic and bone health during perimenopause; and (2) follow the third generation of participants (children of the children) to study intergenerational effects of in utero exposures. TRIAL REGISTRATION NUMBER: NCT00558623.

Lead in candy consumed and blood lead levels of children living in Mexico City.

BACKGROUND: Recent studies have shown that lead exposure continues to pose a health risk in Mexico. Children are a vulnerable population for lead effects and Mexican candy has been found to be a source of exposure in children. There are no previous studies that estimates lead concentrations in candy that children living in Mexico City consume and its association with their blood lead level. OBJECTIVES: To evaluate whether there is an association between reported recent consumption of candies identified to have lead, and blood lead levels among children in Mexico City. METHODS: A subsample of 171 children ages 2-6 years old, from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohort study was assessed between June 2006 and July 2007. The candy reported most frequently were analyzed for lead using ICP-MS. The total weekly intake of lead through the consumption of candy in the previous week was calculated. Capillary blood lead levels (BLL) were measured using LeadCare (anodic stripping voltammetry). RESULTS: Lead concentrations ≥0.1ppm, the FDA permitted level (range: 0.13-0.7ppm) were found in 6 samples out of 138 samples from 44 different brands of candy. Median BLL in children was 4.5µg/dl. After adjusting for child's sex, age, BMI, maternal education & occupation, milk consumption, sucking the candy wrapper, use of lead-glazed pottery, child exposure behavior, living near a lead exposure site and use of folk remedies, an increase of 1µg of lead ingested through candy per week was associated with 3% change (95% CI: 0.1%, 5.2%) in BLL. CONCLUSIONS: Although lead concentrations in candy were mostly below the FDA permitted level, high lead concentrations were detected in 4% of the candy samples and 12% of brands analyzed. Although candy intake was modestly associated with children's BLL, lead should not be found in consumer products, especially in candy that children can consume due to the well documented long-lasting effect of lead exposure.

Maternal MTHFR genotype and haplotype predict deficits in early cognitive development in a lead-exposed birth cohort in Mexico City.

BACKGROUND: Maternal folate nutritional status and prenatal lead exposure can influence fetal development and subsequent health. The methylenetetrahydrofolate reductase (MTHFR) gene is important for folate metabolism, and 2 common polymorphisms, C677T and A1298C, reduce enzymatic activity; C677T is present at high penetrance in Mexican populations. OBJECTIVE: The objective of this study was to examine potential links between maternal and child MTHFR polymorphisms and child neurodevelopment in a lead-exposed population. DESIGN: Data regarding MTHFR polymorphisms C677T and A1298C, peri- and postnatal lead measures, and Bayley Mental Development Index at 24 mo of age (MDI-24) scores were available for 255 mother-child pairs who participated in the ELEMENT (Early Life Exposures in Mexico to Environmental Toxicants) study during 1994-1995. RESULTS: In covariate-adjusted regression models, maternal MTHFR 677 genotype predicted MDI-24 scores, in which each copy of the maternal MTHFR 677T variant allele was associated with lower MDI-24 scores (beta = -3.52; 95% CI: -6.12, -0.93; P = 0.004). Maternal MTHFR haplotype also predicted MDI-24 scores (mean +/- SE: 93.3 +/- 1.2 for 677C-1298A compared with 89.9 +/- 0.8 for 677T-1298A; P < 0.05). MDI-24 scores were not associated with maternal MTHFR 1298 genotype or child MTHFR genotypes. We did not observe significant MTHFR genotype x lead interactions with respect to any of the subject biomarkers of lead exposure. CONCLUSIONS: The maternal MTHFR 677T allele is an independent predictor of poorer child neurodevelopment at 24 mo. These results suggest that maternal genetic variations in folate metabolism during pregnancy may program offspring neurodevelopment trajectories. Further research is warranted to determine the generalizability of these results across other populations.

Maternal dietary intake of polyunsaturated fatty acids modifies the relationship between lead levels in bone and breast milk.

Whereas dietary fats are known to influence bone mineral density, little is known about their effect on the skeletal stores of lead that are a pervasive source of fetal and infant lead exposure from heightened mobilization during pregnancy and lactation. This cross-sectional study examined the potential influence of maternal dietary intake of saturated and unsaturated fats on the relationship of lead levels in bone and breast milk during lactation. Lead was measured in blood, breast milk, and bone (patella and tibia) at 1 mo postpartum in 310 women in Mexico City. Dietary nutrient intake was assessed using a validated FFQ. Multivariate linear regression analyses were used to study the influence of dietary saturated and unsaturated fats on the association between bone and breast milk lead. In multivariate models that included both the dietary intake of SFA and PUFA, an interquartile range increase in patella lead [approximately 20 microg/g (0.097 micromol/g)] was associated with a 24% (95% CI = 5-43) higher increase in breast milk lead in women in the lowest tertile of PUFA intake compared with those in the highest tertile of PUFA intake. Monounsaturated fatty acids did not modify the relationship between lead levels in patella and breast milk. In conclusion, higher maternal dietary intake of PUFA may limit the transfer of lead from bone to breast milk.

Influence of maternal bone lead burden and calcium intake on levels of lead in breast milk over the course of lactation.

The authors studied 367 women who were breastfeeding their infants in Mexico City, Mexico, between 1994 and 1995 to evaluate the effect of cumulative lead exposure, breastfeeding practices, and calcium intake on breast milk lead levels over the course of lactation. Maternal blood and breast milk lead levels were measured at 1, 4, and 7 months postpartum. Bone lead measurements were obtained at 1 month postpartum. At 1, 4, and 7 months postpartum, respectively, the mean breast milk lead levels were 1.4 (standard deviation (SD), 1.1), 1.2 (SD, 1.0), and 0.9 (SD, 0.8) microg/liter and showed a significant decreasing trend over the course of lactation (p < 0.00001). The relations of bone lead and blood lead to breast milk lead were modified by breastfeeding practice, with the highest breast milk lead levels among women with a high level of patella lead who were exclusively breastfeeding. Dietary calcium supplementation increased the rate of decline in breast milk lead by 5-10%, in comparison with a placebo, over the course of lactation, suggesting that calcium supplementation may constitute an important intervention strategy, albeit with a modest effect, for reducing lead in breast milk and thus the potential for exposure by infants.

Omega-3 fatty acid prevents heart rate variability reductions associated with particulate matter.

CONTEXT: Environmental exposure to particulate matter of 2.5 microm or less (PM2.5) has been associated with changes in heart rate variability (HRV). OBJECTIVE: To evaluate the effect of supplementation with omega-3 polyunsaturated fatty acids on the reduction of HRV associated with PM2.5 exposure. DESIGN: Randomized double-blind trial. SETTING: Mexico City, Mexico. PARTICIPANTS: 50 nursing home residents older than 60 yr. INTERVENTION: Randomization to either 2 g/d of fish oil versus 2 g/d of soy oil as the control, with 6 mo follow-up (1-mo presupplementation and 5-mo supplementation) or repeated HRV measurements. PM2.5 was monitored indoors and outdoors. MAIN OUTCOME MEASURE: The association between HRV and 1 SD change in PM2.5 (8 microg/m3). RESULTS: In the group receiving fish oil, the reduction in HRV-high-frequency log(10)-transformed associated with a 1-SD change in PM2.5 was -54% (95% confidence interval, -72, -24) in the presupplementation phase, and only -7% (95% confidence interval, -20,+7) in the supplementation phase (p < 0.01 for the effect of supplementation), with changes in other HRV parameters also being significantly less pronounced during supplementation. Small decreases in PM2.5-associated reductions in HRV parameters also occurred in the group receiving soy oil, but these were not significant. Fish oil supplementation was significantly better in preventing the reduction in percentage of successive normal RR intervals differing by more than 50 ms (p = 0.03) and the root square of the mean of the sum of the squares of differences between adjacent intervals (p = 0.05) than soy oil supplementation. INTERPRETATION: Supplementation with 2 g/d of fish oil prevented HRV decline related to PM2.5 exposure in the study population.

Impact of bone lead and bone resorption on plasma and whole blood lead levels during pregnancy.

The authors tested the hypotheses that maternal bone lead burden is associated with increasing maternal whole blood and plasma lead levels over the course of pregnancy and that this association is modified by rates of maternal bone resorption. A total of 193 Mexican women were evaluated (1997-1999) in the first, second, and third trimesters of pregnancy. Whole blood lead and plasma lead levels were measured in each trimester. Urine was analyzed for cross-linked N-telopeptides (NTx) of type I collagen, a biomarker of bone resorption. Patella and tibia lead levels were measured at 4 weeks postpartum. The relation between whole blood, plasma, and bone lead and NTx was assessed using mixed models. Plasma lead concentrations followed a U-shape, while NTx levels increased significantly during pregnancy. In a multivariate model, the authors observed a significant and positive interaction between NTx and bone lead when plasma lead was used as the outcome variable. Dietary calcium intake was inversely associated with plasma lead. Results for whole blood lead were similar but less pronounced. These results confirm previous evidence that bone resorption increases during pregnancy, with a consequential significant release of lead from bone, constituting an endogenous source of prenatal exposure. They also provide a rationale for testing strategies (e.g., nutritional supplementation with calcium) aimed at decreasing prenatal lead exposure.

Antioxidant supplementation and lung functions among children with asthma exposed to high levels of air pollutants.

To evaluate whether acute effects of ozone, nitrogen dioxide, and particulates with mass median diameter less than 10 micro m could be attenuated by antioxidant vitamin supplementation, we conducted a randomized trial using a double-blinded design. Children with asthma (n = 158) who were residents of Mexico City were randomly given a daily supplement of vitamins (50 mg/day of vitamin E and 250 mg/day of vitamin C) or a placebo and were followed from October 1998 to April 2000. Pulmonary function tests were carried out twice a week in the morning. During the follow-up observation period, the mean 1-hour maximum ozone level was 102 ppb (SD = 47), and the mean 24-hour average PM(10) level was 56.7 micro g/m(3) (SD = 27.4). In children with moderate and severe asthma, ozone levels 1 day before spirometry were inversely associated significantly with forced expiratory flow (FEF(25-75)) (-13.32 ml/second/10 ppb; p = 0.000), FEV(1) (-4.59 ml/10 ppb; p = 0.036), and peak expiratory flow (PEF) (-15.01 ml/second/10 ppb; p = 0.04) in the placebo group after adjusting for potential confounding factors. No association between ozone and lung functions was observed in the supplement group. We observed significant differences in lung function decrements between groups for FEF(25-75) and PEF. Our results suggest that supplementation with antioxidants might modulate the impact of ozone exposure on the small airways of children with moderate to severe asthma.