Prenatal urinary concentrations of phthalate metabolites and behavioral problems in Mexican children: The Programming Research in Obesity, Growth Environment and Social Stress (PROGRESS) study.

BACKGROUND: Phthalate exposure has been associated with increased childhood behavioral problems. Existing studies failed to include phthalate replacements and did not account for high correlations among phthalates. Phthalates' exposure is higher in Mexico than in U.S. locations, making it an ideal target population for this study. AIM: To examine associations between 15 maternal prenatal phthalate metabolite concentrations and children's behavioral problems. METHODS: We quantified phthalate metabolites in maternal urine samples from maternal-child dyads (n = 514) enrolled in the Programming Research in Obesity, Growth Environment and Social Stress (PROGRESS) birth cohort in Mexico City. We performed least absolute shrinkage and selection operator (LASSO) regressions to identify associations between specific-gravity adjusted log2-transformed phthalate metabolites and parent-reported 4-6 year old behavior on the Behavior Assessment System for Children (BASC-2), accounting for metabolite correlations. We adjusted for socio-demographic and birth-related factors, and examined associations stratified by sex. RESULTS: Higher prenatal mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) urinary concentrations were associated with increased hyperactivity scores in the overall sample (ß = 0.57, 95% CI = 0.17, 1.13) and in girls (ß = 0.54, 95% CI = 0.16, 1.08), overall behavioral problems in boys (ß = 0.58, 95% CI = 0.20, 1.15), and depression scores in boys (ß = 0.44, 95% CI = 0.06, 0.88). Higher prenatal monobenzyl phthalate (MBzP) concentrations were associated with reduced hyperactivity scores in girls (ß = -0.54, 95% CI = -1.08, -0.21). DISCUSSION: Our findings suggested that prenatal concentrations of phthalates and their replacements altered child neurodevelopment and those associations may be influenced sex.

Particulate matter exposure, dietary inflammatory index and preterm birth in Mexico city, Mexico.

BACKGROUND: Particulate matter ≤10 µm in aerodynamic diameter (PM10) and diet quality are risk factors for systemic inflammation, which is associated with preterm birth (PTB). PM10 and a pro-inflammatory diet (assessed by the Dietary Inflammatory Index [DII®]) have been individually evaluated as causes of PTB and differences by offspring sex have been reported for the DII. However, additional studies are needed to evaluate joint effects of these associations to inform intervention efforts. OBJECTIVES: To evaluate the independent and joint effects of PM10 and energy-adjusted DII (E-DII) on PTB risks. METHODS: PM10 estimates were generated from daily citywide averages for 1216 pregnant women from three subcohorts of the Early Life Exposures in Mexico to Environmental Toxicants study using data from the Mexico City Outdoor Air Monitoring Network. Among a subset of participants (N = 620), E-DII scores were calculated using a validated food frequency questionnaire. Cox Proportional Hazards models were run for select periods during pregnancy and entire pregnancy averages for E-DII and PM10. We assessed for potential non-linear associations using natural splines. RESULTS: In adjusted models, PM10 exposure was associated with increased risks of PTB for a range of values (58-72 µg/m3) during the second trimester, while negative associations were seen during the second (≥74 µg/m3) and third trimesters (55-65 µg/m3). Analyses conducted using distributed lag models for periods closer to delivery (max lag = 90) did not show negative associations between PM10 exposure and preterm birth, and indeed positive significant associations were observed (estimates and figures). E-DII was not associated with PTB and there was no evidence of effect modification by infant sex. There was no evidence of interaction between PM10 and E-DII and the risk of preterm birth. DISCUSSION: Associations between PM10 and PTB in Mexico City varied over time and across levels of PM10. Our findings of negative associations in the second and third trimesters, which are contrary to the hypothesized relationship between PM10 and PTB, may be due to a number of factors, including live birth bias and the exposure period evaluated. Differences in results for the periods evaluated suggest that PM10 from shorter exposure windows may play a more proximal role in initiating preterm labor.

Phthalate exposure during pregnancy and long-term weight gain in women.

BACKGROUND: Phthalates are known endocrine disruptors and peroxisome proliferator-activated receptor (PPAR) activators, potentially capable of promoting an obesogenic effect. Pregnant women are especially vulnerable to phthalate exposure due to physiological and metabolic changes during pregnancy, including those related to the metabolism of xenobiotics. Phthalate exposure during pregnancy has been associated with early gestational weight gain, however, its effect on long-term weight gain remains unclear. The aim of the present study was to evaluate the association between phthalate exposure during pregnancy and long-term changes in weight among women. METHODS: Urinary phthalate concentrations, socioeconomic, anthropometry and information on diet and socioeconomic status were collected during pregnancy from 178 women from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort. Maternal body weight and diet information was also collected up to 5 times in the first year postpartum and twice during follow-up visits 5.2-10.7 years later. A path analysis was performed to assess associations between urinary phthalate metabolite levels during pregnancy and change in weight (kg) per year after delivery, including age, education, living with/without partner, parity, daily energy intake and breastfeeding duration. RESULTS: The mean age at pregnancy was 27.3 ±â€¯5.9 years and mean body mass index during the first postpartum year was 27.07 ±â€¯4.22 kg/m2. On average, women gained 3.48 kg (0.52 ±â€¯0.84 kg/year). A unit increase in log-transformed mono-3-carboxypropyl phthalate (MCPP) was associated with 0.33 kg (95% CI: 0.09, 0.56) higher weight gain per year, and mono-benzyl phthalate (MBzP) with 0.21 kg (95% CI: -0.38, -0.03) lower weight gain per year. CONCLUSION: Exposure to certain phthalates during pregnancy may be associated with long-term weight change in women. More studies on the effects of phthalate exposure during pregnancy on women's long-term health are required.

Fluoxetine for adults who are overweight or obese.

BACKGROUND: Fluoxetine is a serotonin reuptake inhibitor indicated for major depression. It is also thought to affect weight control: this seems to happen through appetite changes resulting in decreased food intake and normalisation of unusual eating behaviours. However, the benefit-risk ratio of this off-label medication is unclear. OBJECTIVES: To assess the effects of fluoxetine for overweight or obese adults. SEARCH METHODS: We searched the Cochrane Library, MEDLINE, Embase, LILACS, the ICTRP Search Portal and ClinicalTrials.gov and World Health Organization (WHO) ICTRP Search Portal. The last date of the search was December 2018 for all databases, to which we applied no language restrictions . SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing the administration of fluoxetine versus placebo, other anti-obesity agents, non-pharmacological therapy or no treatment in overweight or obese adults without depression, mental illness or abnormal eating patterns. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts and titles for relevance. Screening for inclusion, data extraction and risk of bias assessment was performed by one author and checked by the second. We assessed trials for the overall certainty of the evidence using the GRADE instrument. For additional information we contacted trial authors by email. We performed random-effects meta-analyses and calculated the risk ratio (RR) with 95% confidence intervals (95% CI) for dichotomous outcomes and the mean difference (MD) with 95% CI for continuous outcomes. MAIN RESULTS: We identified 1036 records, scrutinized 52 full-text articles and included 19 completed RCTs (one trial is awaiting assessment). A total of 2216 participants entered the trials, 1280 participants were randomly assigned to fluoxetine (60 mg/d, 40 mg/d, 20 mg/d and 10 mg/d) and 936 participants were randomly assigned to various comparison groups (placebo; the anti-obesity agents diethylpropion, fenproporex, mazindol, sibutramine, metformin, fenfluramine, dexfenfluramine, fluvoxamine, 5-hydroxy-tryptophan; no treatment; and omega-3 gel). Within the 19 RCTs there were 56 trial arms. Fifteen trials were parallel RCTs and four were cross-over RCTs. The participants in the included trials were followed up for periods between three weeks and one year. The certainty of the evidence was low or very low: the majority of trials had a high risk of bias in one or more of the risk of bias domains.For our main comparison group - fluoxetine versus placebo - and across all fluoxetine dosages and durations of treatment, the MD was -2.7 kg (95% CI -4 to -1.4; P < 0.001; 10 trials, 956 participants; low-certainty evidence). The 95% prediction interval ranged between -7.1 kg and 1.7 kg. The MD in body mass index (BMI) reduction across all fluoxetine dosages compared with placebo was -1.1 kg/m² (95% CI -3.7 to 1.4; 3 trials, 97 participants; very low certainty evidence). Only nine placebo-controlled trials reported adverse events. A total of 399 out of 627 participants (63.6%) receiving fluoxetine compared with 352 out of 626 participants (56.2%) receiving placebo experienced an adverse event. Random-effects meta-analysis showed an increase in the risk of having at least one adverse event of any type in the fluoxetine groups compared with placebo (RR 1.18, 95% CI 0.99 to 1.42; P = 0.07; 9 trials, 1253 participants; low-certainty evidence). The 95% prediction interval ranged between 0.74 and 1.88. Following fluoxetine treatment the adverse events of dizziness, drowsiness, fatigue, insomnia and nausea were observed approximately twice as often compared to placebo. A total of 15 out of 197 participants (7.6%) receiving fluoxetine compared with 12 out of 196 participants (6.1%) receiving placebo experienced depression. The RR across all fluoxetine doses compared with placebo was 1.20 (95% CI 0.57 to 2.52; P = 0.62; 3 trials, 393 participants; very low certainty evidence). All-cause mortality, health-related quality of life and socioeconomic effects were not reported.The comparisons of fluoxetine with other anti-obesity agents (3 trials, 234 participants), omega-3 gel (1 trial, 48 participants) and no treatment (1 trial, 60 participants) showed inconclusive results (very low certainty evidence). AUTHORS' CONCLUSIONS: Low-certainty evidence suggests that off-label fluoxetine may decrease weight compared with placebo. However, low-certainty evidence suggests an increase in the risk for dizziness, drowsiness, fatigue, insomnia and nausea following fluoxetine treatment.

Use of Fluoxetine to Reduce Weight in Adults with Overweight or Obesity: Abridged Republication of the Cochrane Systematic Review.

INTRODUCTION: Using fluoxetine is one of many weight loss strategies. A serotonin reuptake inhibitor indicated for depression believed to impact weight control by changing an individual's appetite; however, its benefit-risk ratio is unclear. The aim of this review was to assess the efficacy and safety of fluoxetine in reducing weight in adults with overweight or obesity. METHODS: We searched Cochrane Library, MEDLINE, Embase, and other databases without language restrictions. Cochrane Collaboration tool and GRADE instrument assessed the risk of bias of randomized controlled trials and certainty of their evidence. We conducted random-effects meta-analyses and calculated the risk ratio/mean difference with 95% confidence intervals for the outcomes. RESULTS: We included 19 trials (2,216 adults) and found that fluoxetine may reduce weight by -2.7 kg (95% CI -4 to -1.4; p < 0.001) and body mass index by -1.1 kg/m2 (95% CI -3.7 to 1.4), compared with placebo; however, it would cause approximately twice as many adverse events, such as dizziness, drowsiness, fatigue, insomnia, or nausea. CONCLUSIONS: Although low-certainty evidence suggests that off-label fluoxetine may reduce weight, high-certainty research is needed to be conducted in the future to determine its effects exclusively as well as whether it is useful when combined with other agents. This article is based on a Cochrane Review published in the Cochrane Database of Systematic Reviews 2019, Issue 10, DOI: 10.1002/14651858.CD011688.pub2. Cochrane Reviews are regularly updated as new evidence emerges, and in response to feedback, it should be consulted for the most recent version of the review.

Metabolomics reveals sex-specific pathways associated with changes in adiposity and muscle mass in a cohort of Mexican adolescents.

BACKGROUND: Alterations in body composition (BC) during adolescence relates to future metabolic risk, yet underlying mechanisms remain unclear. OBJECTIVES: To assess the association between the metabolome with changes in adiposity (body mass index [BMI], waist circumference [WC], triceps skinfold [TS], fat percentage [BF%]) and muscle mass (MM). METHODS: In Mexican adolescents (n = 352), untargeted serum metabolomics was profiled at baseline. and data were reduced by pairing hierarchical clustering with confirmatory factor analysis, yielding 30 clusters with 51 singleton metabolites. At the baseline and follow-up visits (1.6-3.5 years apart), anthropometry was collected to identify associations between baseline metabolite clusters and change in BC (∆) using seemingly unrelated and linear regression. RESULTS: Between visits, MM increased in boys and adiposity increased in girls. Sex differences were observed between metabolite clusters and changes in BC. In boys, aromatic amino acids (AAA), branched chain amino acids (BCAA) and fatty acid oxidation metabolites were associated with increases in ∆BMI, and ∆BF%. Phospholipids were associated with decreases in ∆TS and ∆MM. Negative associations were observed for ∆MM in boys with a cluster including AAA and BCAA, whereas positive associations were found for a cluster containing tryptophan metabolites. Few associations were observed between metabolites and BC change in girls, with one cluster comprising methionine, proline and lipids associated with decreases in ∆BMI, ∆WC and ∆MM. CONCLUSION: Sex-specific associations between the metabolome and change in BC were observed, highlighting metabolic pathways underlying adolescent physical growth.

Duration, timing, and consistency of sleep in relation to inflammatory cytokines in Mexican adolescents.

OBJECTIVE: To evaluate whether sleep duration, timing, and variability were associated with inflammatory cytokines in a cohort of Mexico City adolescents. METHODS: The analytic sample comprised >500 adolescents who were part of an ongoing longitudinal study in Mexico City. At two time points during mid-to-late puberty (average age 14, n = 391) and late-to-post puberty (average age 16, n = 345), adolescents completed a follow-up visit that included 7-day wrist actigraphy and clinical assessment of plasma inflammatory cytokines (high-sensitivity C-reactive protein, Interleukin 1ß, Interleukin 6, and Tumor Necrosis Factor ɑ). Sleep characteristics included weekday and weekend sleep duration and midpoint (median of bed and wake time), as well as sleep variability (SD of sleep duration across 7 days) and social jetlag (midpoint difference from weekdays to weekends). At each time point, multivariable linear regression models were run with log inflammatory levels as the outcome and categories of sleep characteristics as predictors, while adjusting for potential confounders (specific to each model). Analyses were run unstratified and sex-stratified. RESULTS: In the mid-to-late pubertal visit, weekday sleep duration was inversely associated with natural log hs-CRP after adjustment (Q4 vs Q1: ß = -0.41, 95% Confidence Interval (CI) -0.81 to -0.01) and later sleep midpoint was positively associated with log hs-CRP (Q4 vs Q1: ß = 0.55, 95% CI 0.13 to 0.97). Sleep duration variability was associated with higher IL-1ß among boys, while in girls social jetlag was associated with higher IL-1ß and weekend sleep duration was inversely associated with IL-6. At the late-to-post pubertal visit, there were few associations except for a positive association between weekday sleep duration and hs-CRP among boys (ß = 0.60, 95% CI 0.04 to 1.16) and a non-linear positive association between social jetlag and hs-CRP among girls (ß = 0.80, 95% CI 0.22 to 1.37 comparing 2 to 3 h of social jetlag vs <1 h). CONCLUSION: Later timing, shorter duration, and inconsistency of sleep were related to higher levels of inflammatory biomarkers, but associations were more evident at the mid-to-late pubertal visit than the late-to-post pubertal visit.

Zinc Supplementation and Fortification in Mexican Children.

BACKGROUND: Zinc is an essential micronutrient for human health. Approximately 1.4% of deaths worldwide are related to zinc deficiency. In Mexico, 33% of children younger than 5 years are zinc deficient. OBJECTIVE: To give an overview of zinc supplementation and fortification in children younger than 5 years through the analysis of current regulations in Mexico, the availability of these products, and the opinion of Mexican experts in this field. METHODS: We gave an overview of zinc supplementation and fortification strategies in the Mexican pediatric population by conducting a literature review of Mexican studies and national standards concerning zinc supplementation and fortification. Semistructured interviews were conducted with personnel from the main producers of zinc supplements and fortified products and from social assistance programs in Mexico. RESULTS: Zinc supplementation in Mexico has been associated with reduction in the duration and incidence of diarrhea. Through interviews with experts, we identified several barriers in achieving adequate zinc consumption such as problems in social assistance programs that distribute zinc-fortified foods, lack of specific dietary recommendations regarding the intake of zinc, lack of regulation of nonpatented zinc supplements, and inconsistencies in public health actions due to political and administrative changes. CONCLUSION: Despite current regulation and efforts made by social assistance programs, zinc deficiency continues to be a prevalent public health issue. Mexico requires an in-depth analysis of existing barriers and alternatives in order to reduce zinc deficiency.

Greater cumulative exposure to a pro-inflammatory diet is associated with higher metabolic syndrome score and blood pressure in young Mexican adults.

Low-grade inflammation is a suggested mechanism in the development of metabolic syndrome (MetS), and diet could act as a regulator. Therefore, we hypothesized that the cumulative Dietary Inflammatory Index (DII®) exposure from diet during infancy through adulthood would be positively associated with the MetS and its components in young Mexican adults. One hundred participants from the Early Life Exposures in Mexico to Environmental Toxicants cohort were included in this analysis. The dietary inflammatory potential of the diet (without supplements) was assessed using 27 nutrients obtained from repeated food frequency questionnaires (1-22 years) using the DII, a validated score. The cumulative exposure of DII was constructed using the area under the curve (AUC of DII). The MetS was defined using the International Diabetes Federation criteria, and the Metabolic Syndrome Risk Z-score (MetRisk Z-score) was estimated. Linear regressions were conducted to assess the association between the AUC of DII with MetRisk Z-score and MetS components, adjusting for sex, socioeconomic status, smoking status, physical activity, birth weight, and body mass index. In adulthood, the mean age was 21.5 years, 54% were male, and 17% had MetS. Positive associations were found between AUC of DII with MetRisk Z-score (ß = .12; 95% confidence interval [CI]: 0.03-0.22; P = .009) and systolic (ß = .33; 95% CI: 0.05-0.61; P = .023) and diastolic blood pressure (ß = .24; 95% CI: 0.01-0.47; P = .040). A cumulative proinflammatory diet from infancy through young adulthood is associated with higher MetRisk Z-scores as well as blood pressure. These findings may provide evidence for the implementation of anti-inflammatory diet interventions throughout early life for the prevention of cardiometabolic risk.

Determinants and characterization of exposure to phthalates, DEHTP and DINCH among pregnant women in the PROTECT birth cohort in Puerto Rico.

BACKGROUND: As a result of evidence suggesting phthalate toxicity, their use has decreased in recent years. However, new phthalates and non-phthalate replacements have emerged in their place, with unknown potential impacts on health. METHODS: We measured 15 phthalate, two di(2-ethylhexyl)terephthalate (DEHTP), and two di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) urinary metabolites, collected up to three times during pregnancy from 994 women in Northern Puerto Rico (2011-2017). We used tests of linear trend to assess changes in concentrations over time and linear mixed models to identify predictors of exposure (sociodemographic characteristics, drinking water sources, diet, product use). RESULTS: Several phthalate metabolites decreased over the study period indicating decreased exposure, while the geometric mean of DEHTP metabolites (molecular sum) increased threefold between 2014 and 2017. Intraclass correlations revealed low to moderate reproducibility of these biomarkers across pregnancy. Several metabolites were associated with maternal age, income, education, pre-pregnancy BMI, drinking public water, use of cleaning and personal care products, and ice cream consumption. DINCH metabolite concentrations remained low throughout the study period. CONCLUSION: Although exposure to some phthalates may be decreasing, exposure to replacements, such as DEHTP, is increasing. Additional studies are needed to further characterize sources of phthalate replacement chemicals and potential exposure-related health effects among vulnerable populations.

Improvement of cardiometabolic markers after fish oil intervention in young Mexican adults and the role of PPARα L162V and PPARγ2 P12A.

Polyunsaturated fatty acids (PUFA) contained in fish oil (FO) are ligands for peroxisome proliferator-activated receptors (PPAR) that may induce changes in cardiometabolic markers. Variation in PPAR genes may influence the beneficial responses linked to FO supplementation in young adults. The study aimed to analyze the effect of FO supplementation on glucose metabolism, circulating lipids and inflammation according to PPARα L162V and PPARγ2 P12A genotypes in young Mexican adults. 191 young, non-smoking subjects between 18 and 40 years were included in a one-arm study. Participants were supplemented with 2.7 g/day of EPA+DHA, during six weeks. Dietary analysis, body composition measurements and indicators for glucose metabolism, circulating lipids, and markers for inflammation were analyzed before and after intervention. An overall decrease in triglycerides (TG) and an increase in HS-ω3 index were observed in all subjects [-4.1 mg/dL, (SD:±51.7), P=.02 and 2.6%, (SD:±1.2), P<.001 respectively]. Mean fasting insulin and glycated hemoglobin (HbA1c%) were significantly decreased in all subjects [-0.547mlU/L, (SD:±10.29), P=.034 and-0.07%, (SD:±0.3), P<.001 respectively], whereas there was no change in body composition, fasting glucose, adiponectin and inflammatory markers. Subjects carrying the minor alleles of PPARα L162V and PPARγ2 P12A had higher responses in reduction of TG and fasting insulin respectively. Interestingly, doses below 2.7 g/day (1.8 g/day) were sufficient to induce a significant reduction in fasting insulin and HbA1c% from baseline (P=.019 and P<.001). The observed responses in triglycerides and fasting insulin in the Mexican population give further evidence of the importance of FO supplementation in young people as an early step towards the prevention of cardiometabolic disease.

Bone mineral density after bariatric surgery. A systematic review.

PURPOSE: Bone regulation system may be affected after bariatric surgeries, but procedures impact differently to bone mineral density (BMD) and measures restraining bone loss are frequently neglected until clinical consequences become manifest. This is a systematic review aimed to elucidate whether BMD loss is comparable after different bariatric surgeries. MATERIALS AND METHODS: A search of morbid obese adults, undergone to bariatric surgery, with BMD measured by dual-energy X-ray absorptiometry at baseline and after surgery studies was performed in several databases. Studies were assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and COCHRANE Risk of Bias tool. The random model was selected for meta-analysis; heterogeneity was analyzed with T(2), inconsistency (I(2) > 50%) and Chi(2) (p < 0.10). Level of evidence and strength of recommendations were summarized using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE System). RESULTS: Twelve studies met the selection criteria. After one year, reduction in total BMD in patients with mixed surgical procedures was significant: -0.03 g/cm(2) (CI 95% 0.00 to -0.06, p < 0.05). BMD was reduced by -0.12 g/cm(2) (CI 95% -0.10 to -0.15, p < 0.001) in the hip, -0.07 g/cm(2) (CI 95% -0.03 to -0.11, p < 0.001) in the column, and -0.03 g/cm(2) (IC 95% -0.02 to -0.04, p < 0.001) in the forearm, but not in restrictive surgeries. Studies included showed high heterogeneity and low quality of evidence. CONCLUSIONS: Patients undergone to mixed bariatric surgery had significant higher BMD deterioration as demonstrated in this review, suggesting that more attention for preventing fractures is required.

Association between Apolipoprotein E Variants and Obesity-Related Traits in Mexican School Children.

BACKGROUND/AIM: Genetic variation in apolipoprotein E (ApoE) has a key role in lipid metabolism. However, its contribution to the amount and distribution of body fat is under investigation. The aim of this study was to analyze the association between genetic variation in ApoE and obesity-related traits in Mexican school children. MATERIAL AND METHODS: Anthropometric, body composition and physical activity measures were conducted using standard methods in 300 children (177 girls/123 boys) who fulfilled the inclusion criteria. DNA was isolated from saliva. ApoE genotypes were analyzed by allelic discrimination. The association between variation in ApoE and anthropometric and body composition measures was investigated using the General Linear Model. RESULTS: The mean±SD values for age, body mass index (BMI) and waist circumference (WC) were 9.05±0.80 years, 19.01±3.83 and 67.98±10.97 cm, respectively. Approximately 46% of the participants were overweight or obese. A significant association between ApoE isoforms and WC was found after controlling for age, sex and the percentage of physical activity (p=0.025). Significant main effects were found for vigorous physical activity and light physical activity influencing the adiposity-related BMI (p<0.001) and WC (p=0.044), respectively. CONCLUSIONS: Variation in ApoE and physical activity intensity were associated with adiposity-related phenotypes in Mexican school children.