Metabolome-wide association study of the relationship between chlorpyrifos exposure and first trimester serum metabolite levels in pregnant Thai farmworkers.

INTRODUCTION: Organophosphate (OP) insecticides, including chlorpyrifos, have been linked with numerous harmful health effects on maternal and child health. Limited data are available on the biological mechanisms and endogenous pathways underlying the toxicity of chlorpyrifos exposures on pregnancy and birth outcomes. In this study, we measured a urinary chlorpyrifos metabolite and used high-resolution metabolomics (HRM) to identify biological perturbations associated with chlorpyrifos exposure among pregnant women in Thailand, who are disparately exposed to high levels of OP insecticides. METHODS: This study included 50 participants from the Study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE). We used liquid chromatography-high resolution mass spectrometry to conduct metabolic profiling on first trimester serum samples collected from participants to evaluate metabolic perturbations in relation to chlorpyrifos exposures. We measured 3,5,6-trichloro-2-pyridinol (TCPy), a specific metabolite of chlorpyrifos and chlorpyrifos-methyl, in first trimester urine samples to assess the levels of exposures. Following an untargeted metabolome-wide association study workflow, we used generalized linear models, pathway enrichment analyses, and chemical annotation to identify significant metabolites and pathways associated with urinary TCPy levels. RESULTS: In the 50 SAWASDEE participants, the median urinary TCPy level was 4.36 µg TCPy/g creatinine. In total, 691 unique metabolic features were found significantly associated with TCPy levels (p < 0.05) after controlling for confounding factors. Pathway analysis of metabolic features associated with TCPy indicated perturbations in 24 metabolic pathways, most closely linked to the production of reactive oxygen species and cellular damage. These pathways include tryptophan metabolism, fatty acid oxidation and peroxisome metabolism, cytochromes P450 metabolism, glutathione metabolism, and vitamin B3 metabolism. We confirmed the chemical identities of 25 metabolites associated with TCPy levels, including glutathione, cystine, arachidic acid, itaconate, and nicotinamide adenine dinucleotide. DISCUSSION: The metabolic perturbations associated with TCPy levels were related to oxidative stress, cellular damage and repair, and systemic inflammation, which could ultimately contribute to health outcomes, including neurodevelopmental deficits in the child. These findings support the future development of sensitive biomarkers to investigate the metabolic underpinnings related to pesticide exposure during pregnancy and to understand its link to adverse outcomes in children.

Higher maternal BMI early in pregnancy is associated with overweight and obesity in young adult offspring in Thailand.

BACKGROUND: Rates of overweight and obesity among women of reproductive age have been steadily increasing worldwide and in Thailand. There is mounting evidence that maternal obesity during pregnancy is associated with an increased risk of obesity and other adverse health outcomes in the offspring, but such data are lacking for Thailand. We examined the associations between maternal body mass index (BMI) and anthropometry (particularly the likelihood of obesity) and cardiometabolic parameters in young adult offspring. METHODS: This was a prospective follow-up study of a birth cohort in Chiang Mai (Thailand). Pregnant women carrying singletons were recruited at their first antenatal visit (< 24 weeks of gestation) and followed until delivery in 1989-1990. Participants were their young adult offspring followed up in 2010. Maternal BMI was recorded at the first antenatal visit. The offspring underwent clinical assessments, including anthropometry, lipid profile, insulin sensitivity (HOMA-IR), blood pressure, and carotid intima-media thickness. The primary outcome of interest was the likelihood of obesity in the offspring. RESULTS: We assessed 628 young adults (54% were females) at 20.6 ± 0.5 years of age (range 19.1-22.1 years). The young adult offspring of mothers with overweight/obesity was 14.1 kg (95%CI 9.7, 18.5; p < 0.0001) and 9.4 kg (95% CI 6.1, 12.8; p < 0.0001) heavier than those born to mothers with underweight or normal weight, respectively, and had BMI 3.46 kg/m2 (95%CI 2.26, 4.67; p < 0.0001) and 5.27 kg/m2 (95%CI 3.67, 8.68; p < 0.0001) greater, respectively. For every 1-kg/m2 increase in maternal BMI, the adjusted odds ratio (aOR) of offspring obesity was 25% greater (95%CI 1.10, 1.42; p < 0.001). Thus, the aOR of obesity in offspring of mothers with overweight/obesity was 4.6 times greater (95%CI 1.86, 11.26; p < 0.001) and nearly 17-fold greater (95%CI 1.96, 146.4; p = 0.010) compared to young adults born to mothers with normal weight or underweight, respectively. There were no observed associations between maternal BMI status and offspring metabolism or blood pressure. DISCUSSION: Maternal overweight/obesity early in pregnancy was associated with increased BMI and greater odds of obesity in their young adult offspring in Thailand. These findings highlight the public health importance of fostering healthier lifestyle choices among women of reproductive age.

Lower insulin sensitivity in young adults born preterm in Thailand.

BACKGROUND: Previous studies reported impaired glucose homeostasis among preterm survivors, but consisted almost exclusively of Caucasians. It is unknown whether Asians born preterm display similar impairments. AIM: To assess glucose homeostasis and other cardiometabolic outcomes among young adults born preterm in Thailand. METHODS: Participants were 575 young adult offspring of mothers from the Chiang Mai Low Birth Weight Study, born in 1989 to 1990 and followed up in 2010: 54.1% females, median age 20.6 years, including 33 individuals (5.7%) born preterm. After an overnight fast, participants underwent clinical assessments, including blood sampling (glucose, insulin, and lipid profile). Insulin sensitivity was assessed using HOMA-IR and insulin secretion estimated using HOMA-ß. RESULTS: In unadjusted analyses, young Thai adults born preterm were 3.2 cm shorter (P = .037), 6 kg lighter (P = .016), and had HOMA-ß 34% higher (P = .026) than those born at term. Adjusted analyses accounting for important confounders showed marked impairments in glucose homeostasis among preterm survivors: fasting insulin levels were 32% greater (P = .011), with HOMA-IR and HOMA-ß that were 31% (P = .020) and 43% higher (P = .005), respectively, compared to peers born at term. There were no other contrasting observations between groups, with anthropometric differences disappearing after adjustment for confounders. DISCUSSION: Young adults in Thailand born preterm were more insulin resistant than peers born at term. The observed impairments in glucose metabolism among young Thai adults born preterm corroborate findings reported mostly on Caucasians. The challenge for general practitioners and public health professionals is to encourage those born preterm to make healthier lifestyle choices early on.

Contribution of Android and Gynoid Adiposity to Bone Mineral Density in Healthy Postmenopausal Thai Women.

Dual-energy X-ray absorptiometry (DXA) is one of the major tools for assessing the whole body and regional body composition and body adiposity. Various body composition parameters including android fat mass (AFM), gynoid fat mass (GFM), and android-to-gynoid fat ratio (AG fat ratio) obtained from whole body DXA can be used as a reliable surrogate marker for regional body composition analysis. This study aimed to explore the contribution of android and gynoid adiposity to bone mineral density (BMD) in healthy postmenopausal Thai women. This cross-sectional study enrolled 1448 healthy Thai women, ages 40-90 without medication history or known disease affecting the BMD. Lumbar spine (LS), total femur, and femoral neck BMDs, AFM, GFM, and AG fat ratio were measured by DXA. To evaluate the contribution of android and gynoid adiposity with various measures of BMDs, univariable and multivariable linear regression analyses were used to estimate the regression coefficients. AFM, GFM, and AG fat ratio had a significant positive association with BMD of all measured sites (p < 0.001) in the univariate analysis. The strongest association was found between AG fat ratio and LS BMD (ß = 0.156, p ≤ 0.001). In multivariate linear regression analysis, the results continued to show a positive association between AFM and GFM at all skeletal sites after adjusting for age, height, and total body lean mass. Relationship between AG fat ratio and BMD was found only in LS region. GFM had a strongest positive effect with BMD at the LS, total femur, and femoral neck regions. Higher android and gynoid adiposity was associated with higher BMD. GFM rather than AFM shows the strongest positive association with BMDs in postmenopausal Thai women.

Underrecognition and Undertreatment for Peripheral Arterial Disease in Diabetic Patients in Thailand.

Objective: Although several guidelines emphasized the importance of atherosclerotic risk factor management in peripheral arterial disease (PAD) in diabetic patients to reduce the cardiovascular mortality, authors do not know to what extent physicians follow these guidelines. Material and Method: Between May 2014 and August 2014, consecutive eligible outpatients, aged ≥45 years with established DM, were invited to be involved in this study. History, physical exam and laboratory test were reviewed. Ankle brachial index ≤0.9 was considered PAD. Then patients were evaluated the percentage of risk factor control according to American Heart Association (AHA) criteria. The good control was defined that patients have adequate risk factor control between 3-5 factors. Results: 2,247 diabetic patients were recruited for the study. 286 patients out of 2,247 were diagnosed PAD (12.7%). 236 PAD patients (82.5%) did not have any symptom of intermittent claudication, rest pain, gangrene or ulcer. According to AHA criteria, the percentage of adequate control in low density lipoprotein, HbA1C and systolic blood pressure in PAD patients was 18.9, 30.1 and 33.2% respectively. 49.8% in PAD patients had met our good risk factor control criteria. Conclusion: Most PAD in diabetic patients was asymptomatic. The atherosclerotic risk factor control was poor in this group.

Associations of maternal organophosphate pesticide exposure and PON1 activity with birth outcomes in SAWASDEE birth cohort, Thailand.

Prenatal organophosphate (OP) pesticide exposure has been reported to be associated with adverse birth outcomes and neurodevelopment. However, the mechanisms of toxicity of OP pesticides on human fetal development have not yet been elucidated. Our pilot study birth cohort, the Study of Asian Women and Offspring's Development and Environmental Exposures (SAWASDEE cohort) aimed to evaluate environmental chemical exposures and their relation to birth outcomes and infant neurodevelopment in 52 pregnant farmworkers in Fang district, Chiang Mai province, Thailand. A large array of data was collected multiple times during pregnancy including approximately monthly urine samples for evaluation of pesticide exposure, three blood samples for pesticide-related enzyme measurements and questionnaire data. This study investigated the changes in maternal acetylcholinesterase (AChE) and paraoxonase 1 (PON1) activities and their relation to urinary diakylphosphates (DAPs), class-related metabolites of OP pesticides, during pregnancy. Maternal AChE, butyrylcholinesterase (BChE) and PON1 activities were measured three times during pregnancy and urinary DAP concentrations were measured, on average, 8 times from enrollment during pregnancy until delivery. Among the individuals in the group with low maternal PON1 activity (n=23), newborn head circumference was negatively correlated with log10 maternal ∑DEAP and ∑DAP at enrollment (gestational age=12±3 weeks; ß=-1.0 cm, p=0.03 and ß=-1.8 cm, p<0.01, respectively) and at 32 weeks pregnancy (ß=-1.1cm, p=0.04 and ß=-2.6 cm, p=0.01, respectively). Furthermore, among these mothers, newborn birthweight was also negatively associated with log10 maternal ∑DEAP and ∑DAP at enrollment (ß=-219.7 g, p=0.05 and ß=-371.3g, p=0.02, respectively). Associations between maternal DAP levels and newborn outcomes were not observed in the group of participants with high maternal PON1 activity. Our results support previous findings from US birth cohort studies. This is the first study to report the associations between prenatal OP pesticide exposure and birth outcomes in Thailand.

Determination of the pyrethroid insecticide metabolite 3-PBA in plasma and urine samples from farmer and consumer groups in northern Thailand.

In this study, the enzyme-linked immunosorbent assays (ELISA) were modified to detect 3-PBA in plasma (including the adducted form) and urine among a large group of consumers and farmers in an agricultural area. The samples were collected on the same day in the morning from 100 consumers (50 females, 50 males) and 100 farmers (50 females, 50 males) in the Fang district, Chiang Mai province, northern Thailand. The ELISA was very sensitive having an IC50 value of 26.7 and 15.3 ng/mL, a limit of quantitation of 5 and 2.5 ng/mL and a limit of detection of 1.08 and 1.94 ng/mL for plasma and urine, respectively. These methods had low (< 5%) intra- and inter-assay coefficients of variation. The extraction technique satisfactorily eliminated the matrix effect from samples before ELISA analysis, yielding good recoveries (85.9-99.4% and 87.3-98.0%, respectively). For the volunteer study, the detection rate for plasma 3-PBA was 24% in consumers and 42% in farmers, but the median and range values were similar (median 5.87 ng/mL, range 5.16-8.44 ng/mL in consumers and 6.27 ng/mL, range 4.29-9.57 ng/mL in farmers). The rate of detection in the urine was similar (76% and 69%, in consumers and in farmers), yet the median concentration was significantly higher in farmers (8.86 µg/g creatinine in consumers vs 16.1 µg/g creatinine in farmers) and the range also much wider in farmers (1.62-80.5 µg/g creatinine in consumers and 0.80-256.2 µg/g creatinine in farmers). There was no correlation between plasma 3-PBA and urinary 3-PBA concentrations in the study presumably because plasma 3-PBA is a measure of cumulative exposures while urinary 3-PBA reflects acute exposures. In addition, metabolism and excretion of pyrethroids varies by individual. Nevertheless, this study demonstrated that these volunteers were exposed to pyrethroids. To our knowledge, this is the first report that compared plasma 3-PBA and urinary 3-PBA in a large group of volunteers. The ELISA method provided higher sample throughput with lower cost as compared to the instrumental analysis.

Chronic Kidney Disease Predicts Adverse Major Cardiovascular Events and Adverse Limb Events in Patients With Diabetes and Peripheral Arterial Disease.

This study aims to explore the effect in each stage of chronic kidney disease (CKD) on the major adverse cardiovascular events (MACE) in diabetes mellitus (DM) patients with peripheral arterial disease (PAD). A total of 246 DM patients with diagnosed PAD were enrolled in this study. Of these, 86 patients (35%) died and 34 patients had non-fatal cardiovascular events occurred at the last 7 years follow-up. The baseline eGFR obtained from the first quantified eGFR value within 6 months from the date of enrollment estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Then, based on eGFR at entry, we defined CKD as an eGFR < 60 mL/min/1.73 m2, and stratified all patients into four groups: eGFR-1, normal eGFR (≥90 mL/min/1.73 m2); eGFR-2, mildly decreased eGFR (60-89 mL/min/1.73 m2); eGFR-3, moderately decreased eGFR (30-59 mL/min/1.73 m2); and eGFR-4, severely decreased eGFR (<30 mL/min/1.73 m2). The mean eGFR was 54.4 ± 28.9 mL/min/1.73m2, and more than 30% of all patients had CKD (eGFR <60 mL/min/1.73m2). The seven-year cumulative incidence of MACE was 29.8% (95% confident interval [95% CI] 15.5-35.7) for eGFR-1 group, 40.4% (95% CI 27.4-45.2) for eGFR-2group, 66.2% (95% CI 47.6-71.4) for eGFR-3 group, and 94% (95% CI 75.0-99.0) for eGFR-4 group. In addition, after adjustment, hazard ratio (HR) for MACE was 2.36 (95% CI 1.26-4.40) in the eGFR-3 group and 7.62 (95% CI 3.71-15.66) in the eGFR-4 group. Restricted mean survival time (RMST) for survival analysis was consistent with HR in this study. After adjusting confounders, relative to eGFR-1 group, an association between the eGFR group and MACE outcome was found only in eGFR-3 group and eGFR-4 group. The moderate to severe reduction in eGFR, was an independent risk factor for MACE among DM patients with PAD throughout a 7-year follow-up duration. Thus, early CKD screening might be essential in the management of diabetic patients with PAD.

Associations between maternal overweight/obesity during pregnancy and body composition in young adult offspring.

Background: Maternal obesity is associated with an increased risk of large-for-gestational-age births and childhood obesity. However, evidence on its potential associations with long-term offspring body composition remains limited. This prospective cohort study examined associations between maternal body mass index (BMI) during pregnancy and body composition in the young adult offspring. Methods: Participants were the offspring from a birth cohort in Chiang Mai (Thailand). Maternal BMI was assessed at the first antenatal clinic visit (≤24 weeks of gestation) in 1989-1990. In 2010-2011, we followed up the offspring at approximately 20 years of age, assessing their body composition using whole-body dual-energy X-ray absorptiometry (DXA) scans. Associations between maternal BMI and offspring body composition were explored using unadjusted and adjusted analyses. Results: We assessed 391 young adults (55% were females). Higher maternal BMI was associated with increased offspring fat mass and lean mass. In adjusted analyses, offspring of mothers with overweight/obesity exhibited total body fat percentages 1.5 (95% CI 0.1, 2.9; p = 0.032) and 2.3 (95% CI 0.2, 4.5; p = 0.036) percentage points higher than offspring of normal-weight and underweight mothers, respectively. Fat mass index was similarly higher: 0.9 kg/m2 (95% CI 0.3, 1.5 kg/m2; p = 0.002) and 1.4 kg/m2 (95% CI 0.5, 2.3 kg/m2; p = 0.002), respectively. However, no differences in visceral adiposity were detected. Conclusion: Higher maternal BMI during pregnancy was associated with increased adiposity in young adult offspring. Our findings suggest that the cross-generational transmission of maternal obesity-related traits is associated with increased offspring adiposity in the long term.

Importance of ethnic base standard references for the diagnosis of osteoporosis in Thai women.

Many studies demonstrated the importance of using ethnic-specific normal database in the diagnosis of osteoporosis (OP). Aims of this study were to assess diagnostic agreement, prevalence of OP, and diagnostic misclassification between Caucasian, Japanese, and Thai normal databases. The cross-sectional study of 3181 Thai women who had bone mineral density (BMD) measurement between January 2008 and December 2010 was performed. BMDs at lumbar spine (LS), femoral neck (FN), and total hip (TH) were derived to T-score by using Caucasian, Japanese, and Thai standard references. Kappa statistic was used to assess diagnostic agreement and misclassification. Diagnostic agreements between Caucasian and Thai reference databases were 0.39 for LS and 0.90 for FN. No statistical agreement was found in TH region (0.01, p value=0.264). Applying the Japanese reference, diagnostic agreements were 0.71 for LS, 0.76 for FN, and 0.94 for TH regions. Prevalence of OP in postmenopausal women was 64.1%, 37.7%, and 41.4% using Caucasian, Japanese, and Thai standard references. Percentage of misclassification was varied by menopausal status and reference database from 11.2% to 48.7%. When applying Japanese databases instead of Caucasian normal databases, overall diagnostic misclassification decreased from 35.1% to 16.1%. Choice of reference database has a significant effect on the diagnosis of low bone mass and OP. Japanese reference database has better diagnostic agreement with previously studied Thai reference database in 1999 than Caucasian reference database.

The risk factors of low birth weight infants in the northern part of Thailand.

BACKGROUND: The incidence of low birth weight (LBW) in Chiang Mai University Hospital was high. OBJECTIVE: Determined the incidence and risk factors of low birth weight infants. MATERIAL AND METHOD: The present study included pregnant women between 1989 and 1990 who attended the antenatal clinics (ANC) having a gestational age less than or equal to 24 weeks. During that period, up to delivery, clinical and other potential data namely demographic and biomedical factors, maternal status, socioeconomic factors, and nutritional factors were included. The birth weight at birth less than 2,500 gm was considered LBW. RESULTS: Two thousand one hundred eighty four pregnant subjects who delivered live born and were still eligible, were used for analysis in the present study. The incidence of LBW was 9.2% (201/2,184). Women with body mass index (BMI) at first antenatal clinics (ANC) less than 18.5 Kg/m2 and weight gain during the second trimester less than 300 grams/week was the strongest independent risk factor for LBW (odds ratio 11.25, 95% confidence interval (CI) 5.77-21.94). The number of antenatal care less than 4, monilial vaginitis, the infestation of hookworm and strongyloides, and pregnancy-induced hypertension were independent risk factors (odds ratio 11.04, 3.14, 4.93 and 4.02 respectively). CONCLUSION: The present study showed that low initial BMI, low weight gain in the second trimester, and low attendance at ANC are associated to the occurrence of LBW. The development of a scoring system for detecting high-risk of LBW in pregnant women based on a combination of antenatal factors should be pursued.

Associations between maternal plasma zinc concentrations in late pregnancy and LINE-1 and Alu methylation loci in the young adult offspring.

BACKGROUND: In animal models, prenatal zinc deficiency induced epigenetic changes in the fetus, but data in humans are lacking. We aimed to examine associations between maternal zinc levels during pregnancy and DNA methylation in LINE-1 and Alu repetitive sequences in young adult offspring, as well as anthropometry and cardiometabolic parameters. METHODS: Participants were 74 pregnant women from the Chiang Mai Low Birth Weight cohort, and their offspring followed up at 20 years of age. Maternal plasma zinc concentrations were measured at approximately 36 weeks of gestation. DNA methylation levels in LINE-1 and Alu repetitive sequences were measured in the offspring, as well as anthropometry and cardiometabolic parameters (lipid profile, blood pressure, and glucose metabolism). RESULTS: Over half of mothers (39/74; 53%) were zinc deficient (<50 µg/dL) during their third trimester of pregnancy. Maternal zinc concentrations during pregnancy were associated with LINE-1 DNA methylation levels in adult offspring. Specifically, lower prenatal zinc concentrations were associated with: 1) lower levels of total LINE-1 methylation; 2) lower levels of LINE-1 hypermethylation loci; and 3) higher levels of LINE-1 partial methylation loci. Prenatal zinc concentrations were not associated with Alu methylation levels, nor with any anthropometric or cardiometabolic parameters in adult offspring. However, we observed associations between Alu and LINE-1 methylation patterns and cardiometabolic outcomes in offspring, namely total cholesterol levels and diastolic blood pressure, respectively. CONCLUSIONS: Lower maternal zinc concentrations late in gestation were associated with changes in DNA methylation in later life. Thus, zinc deficiency during pregnancy may induce alterations in total LINE-1 methylation and LINE-1 hypermethylation loci. These results suggest a possible epigenetic link between zinc deficiency during pregnancy and long-term outcomes in the offspring.

Association between Haematological Parameters and Exposure to a Mixture of Organophosphate and Neonicotinoid Insecticides among Male Farmworkers in Northern Thailand.

Exposure to insecticides may result in various health problems. This study investigated the association between haematological parameters and exposure to a mixture of organophosphate (OP) and neonicotinoid (NEO) insecticides among male farmworkers in Fang district, Chiang Mai province, northern Thailand. Concentrations of urinary dialkylphosphates, non-specific metabolites of OPs, and NEOs and their metabolites and haematological parameters were measured in 143 male farmworkers. The Bayesian kernel machine regression model was employed to evaluate the associations. Exposure to a mixture of insecticides was significantly associated with the mean corpuscular haemoglobin concentration (MCHC) when the concentrations of all the compounds and their metabolites were at the 60th percentile or higher compared with the 50th percentile. Furthermore, exposure to clothianidin (CLO) showed a decreasing association with MCHC when all the other insecticides were at their mean concentrations. CLO was the most likely compound to reduce MCHC, and this was confirmed by sensitivity analysis. These findings suggest that exposure to NEO insecticides, especially CLO, affects the haematological status relating to haemoglobin parameters.

Exposure to Organophosphate and Neonicotinoid Insecticides and Its Association with Steroid Hormones among Male Reproductive-Age Farmworkers in Northern Thailand.

Several studies indicated organophosphate (OP) and neonicotinoid (NEO) insecticides are endocrine disruptors; however, data are scarce. This cross-sectional study recruited 143 male farmworkers aged 18-40 years in Fang district, Chiang Mai province, northern Thailand. OP exposure was assessed by measuring urinary dialkylphosphate (DAPs) using a gas-chromatography flame photometric detector. Urinary NEOs, their metabolites (NEO/m) and serum steroid hormones were measured using liquid chromatography-tandem mass spectrometry. Characteristics of participants were determined by face-to-face interviews. DAPs and five NEO/m were detected in more than 60% of samples. The concentration of diethylphosphate was highest among DAP metabolites (geometric mean concentration (GM: 23.9 ng/mL) and the concentration of imidacloprid (IMI) was highest among NEO/m (GM: 17.4 ng/mL). Linear regression models showed that the IMI level was positively associated with testosterone, dehydrocorticosterone (DHC) and dehydroepiandrosterone (DHEA) levels. Imidacloprid-olefin and DHEA levels were positively associated. Thiamethoxam (THX) were inversely associated with DHC and deoxycorticosterone levels. Clothianidin (CLO), THX and N-desmethyl-acetamiprid levels were positively associated with the androstenedione level. CLO and THX levels were inversely associated with the cortisone level. In conclusion, the association between NEO insecticides exposure and adrenal androgens, glucocorticoids and mineralocorticoids, suggest potential steroidogenesis activities. Our findings warrant further investigation.

Caesarean delivery is associated with increased blood pressure in young adult offspring.

We examined the associations between caesarean section (CS) delivery and cardiovascular risk factors in young adults in Thailand. Participants were 632 offspring from a birth cohort in Chiang Mai (Northern Thailand), born in 1989-1990 and assessed in 2010 at a mean age of 20.6 years, including 57 individuals (9.0%) born by CS and 575 born vaginally. Clinical assessments included anthropometry, blood pressure (BP), carotid intima-media thickness, and fasting blood glucose, insulin, and lipid profile. Young adults born by CS had systolic BP (SBP) 6.2 mmHg higher (p < 0.001), diastolic BP 3.2 mmHg higher (p = 0.029), and mean arterial pressure (MAP) 4.1 mmHg higher (p = 0.003) than those born vaginally. After covariate adjustments, SBP and MAP remained 4.1 mmHg (p = 0.006) and 2.9 mmHg (p = 0.021) higher, respectively, in the CS group. The prevalence of abnormal SBP (i.e., pre-hypertension or hypertension) in the CS group was 2.5 times that of those born vaginally (25.0% vs 10.3%; p = 0.003), with an adjusted relative risk of abnormal SBP 1.9 times higher (95% CI 1.15, 2.98; p = 0.011). There were no differences in anthropometry (including obesity risk) or other metabolic parameters. In this birth cohort in Thailand, CS delivery was associated with increased blood pressure in young adulthood.

Birth order is associated with an increased risk of obesity in young adults in Thailand.

BACKGROUND: There is a growing body of evidence showing that early life events are associated with increased risk of cardiovascular and metabolic diseases later in adult life. However, there is a paucity of data in this field from Asian populations. In this study, we examined the association of birth order with obesity risk and cardiometabolic outcomes in young adults in Thailand. METHODS: Participants were the offspring from a birth cohort study in Chiang Mai (northern Thailand), who were followed up at ~20.5 years of age. Clinical assessments included anthropometry, blood pressure, fasting blood samples and carotid intima-media thickness. Insulin sensitivity was estimated using homeostatic model assessment of insulin resistance (HOMA-IR). Participants were stratified into two groups: first-borns and later-borns. Health outcomes between groups were compared using multivariable models adjusting for important confounders, in particular maternal body mass index (BMI). RESULTS: A total of 559 participants were studied: 316 first-borns (46% males) and 243 later-borns (47% males). Adjusted models showed anthropometric differences, with first-borns being 2.3 kg heavier (p=0.023) with a BMI 0.86 kg/m2 greater (p=0.019) than later-borns. Thus, rates of obesity were higher in first-borns than in later-borns (6.6% vs 2.9%), so that first-borns had an adjusted relative risk of obesity 3.3 times greater than later-borns [95% CI 1.42 to 7.88; p=0.006]. There were no observed differences in cardiovascular or metabolic parameters assessed, including HOMA-IR. CONCLUSION: As observed in other populations, first-borns in Thailand had greater BMI and an increased risk of obesity in young adulthood. However, we observed no other cardiometabolic differences between first- and later-borns.

Placental transfer of DDT in mother-infant pairs from Northern Thailand.

The present study objective was to investigate ratios and correlation coefficients between dichlorodiphenyltrichloroethane (DDT) compounds in cord and maternal sera of mother-infant pairs from northern Thailand. The study site was located in Chiang Dao District of Chiang Mai Province which was an agricultural and former malaria endemic area. DDT compounds were analyzed in 88 cord and maternal serum samples using gas chromatography-electron capture detection (GC-ECD). p,p'-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene) was the major component and detected in every cord and maternal serum samples with geometric means of 1,255 and 1,793 n g(-1) lipids, respectively. p,p'-DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane) was detected at 89.8 and 100% of cord and maternal serum samples, respectively. The second and third highest levels detected were p,p'-DDD (1,1-dichloro-2,2-bis(p-chlorophenyl)ethane) and p,p'-DDT, respectively. The ratios between cord and maternal sera for p,p'-DDE, p,p'-DDT, and p,p'-DDD that were less than 1 had high correlation coefficients (ratio = 0.70, r = 0.82 for p,p'-DDE, ratio = 0.62, r = 0.66 for p,p'-DDT, and ratio = 0.79, r = 0.78 for p,p'-DDD). The high correlation coefficients indicate that cord serum levels of DDT compounds could be accurately estimated from maternal serum levels. It can be concluded that cord serum levels of p,p'-DDE, p,p'-DDT, and p,p'-DDD were approximately 70%, 62%, and 79% of maternal serum levels, respectively. Furthermore, our findings can be applied in public health to monitor and evaluate risk among infants from high DDT exposure area.

Lipodystrophy and metabolic changes in HIV-infected children on non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy.

BACKGROUND: Highly active antiretroviral therapy (HAART) has recently been implemented in Thailand. Its long-term effects have not been clearly evaluated. The objective of this study was to estimate the prevalence of lipodystrophy (LD) and other metabolic changes in HIV-infected children receiving HAART. METHODS: Ninety children who began HAART (either nevirapine or efavirenz, together with lamivudine and stavudine) were prospectively followed. LD was assessed by waist-to-hip ratio and LD checklist. Hypercholesterolaemia was defined as total cholesterol > 200 mg/dl and low-density lipoprotein cholesterol > 130 mg/dl. Low levels of high-density lipoprotein cholesterol (HDL-c), hypertriglyceridaemia and hyperglycaemia were defined as HDL-c < 40 mg/dl, triglyceride > 200 mg/dl and plasma glucose > 110 mg/dl, respectively. RESULTS: The mean age at entry was 7.6 (SD 2.9) years. Fifty-three children received nevirapine- and 37 received efavirenz-based HAART. The prevalence of LD was 9%, 47% and 65% at 48, 96 and 144 weeks after HAART initiation, respectively. Patterns of LD at week 144 were central lipohypertrophy (46%), peripheral lipoatrophy (20%), and combined type (34%). A higher prevalence of LD was found among females (61% versus 39%; P = 0.04) and those with more advanced disease (CDC category B or C) at baseline (73% versus 51%; P = 0.04). There was no difference in prevalence of LD between the two regimens. At 144 weeks, fasting hypertriglyceridaemia was detected in 12%, hypercholesterolaemia in 11%, and increased plasma glucose in 4% of children. Low HDL-cholesterolaemia decreased from 94% at baseline to 12% at week 144 (P < 0.01). CONCLUSIONS: More than half of the children developed LD at 144 weeks after HAART. Dyslipidaemia occurred in 11-12% of children.

Efficacy and safety of sildenafil in Asian males with erectile dysfunction and cardiovascular risk.

OBJECTIVE: Assess the effectiveness of sildenafil in Asian males with erectile dysfunction (ED) and one or more of the co-morbidities, mild-to-moderate hypertension, dyslipidemia, and diabetes. MATERIAL AND METHOD: A six-week, double-blind, randomized, placebo-controlled, multicenter study was carried out in Thailand, Malaysia and Singapore. One hundred and fifty five male subjects were randomized (2:1) to sildenafil (n = 104) or placebo (n = 51). Sildenafil was started at 50 mg and increased (100 mg) or decreased (25 mg) at week 2 if necessary. RESULTS: On the primary efficacy endpoint, sildenafil-treated subjects had significantly better scores on the International Index of Erectile Function (IIEF) questions 3 and 4 than placebo (p < 0.001, both questions). When accumulated into IIEF domains, all five domains were significant in favor of sildenafil. In addition, sildenafil-treated subjects were more satisfied with treatment and had a higher intercourse success rate. The majority of adverse events were mild in severity; the most commonly reported treatment-related events were dizziness (7.7%) and tinnitus (2.9%). CONCLUSION: Sildenafil (25, 50, and 100 mg) was found to be an effective, safe, and well-tolerated treatment for ED in the present study population of Thai, Malaysian, and Singaporean males who also had increased cardiovascular risk

Daily Consumption of Virgin Coconut Oil Increases High-Density Lipoprotein Cholesterol Levels in Healthy Volunteers: A Randomized Crossover Trial.

This open-label, randomized, controlled, crossover trial assessed the effect of daily virgin coconut oil (VCO) consumption on plasma lipoproteins levels and adverse events. The study population was 35 healthy Thai volunteers, aged 18-25. At entry, participants were randomly allocated to receive either (i) 15 mL VCO or (ii) 15 mL 2% carboxymethylcellulose (CMC) solution (as control), twice daily, for 8 weeks. After 8 weeks, participants had an 8-week washout period and then crossed over to take the alternative regimen for 8 weeks. Plasma lipoproteins levels were measured in participants at baseline, week-8, week-16, and week-24 follow-up visits. Results. Of 32 volunteers with complete follow-up (16 males and 16 females), daily VCO intake significantly increased high-density lipoprotein cholesterol by 5.72 mg/dL (p = 0.001) compared to the control regimen. However, there was no difference in the change in total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels between the two regimens. Mild diarrhea was reported by some volunteers when taking VCO, but no serious adverse events were reported. Conclusion. Daily consumption of 30 mL VCO in young healthy adults significantly increased high-density lipoprotein cholesterol. No major safety issues of taking VCO daily for 8 weeks were reported.