Ling Chu Chien

The neurological effects of prenatal and postnatal mercury/methylmercury exposure on three-year-old children in Taiwan

This study attempts to elucidate the relationship between neurological effects and mercury/methylmercury concentrations in various biomarkers, including meconium, hair, fingernail, and toenail. Eight-three mother-infant pairs were recruited between August 2008 and December 2009, and follow-up examinations on these children were completed after three years. The Bayley Scales of Infant and Toddler Development (Bayley-III) for evaluating the cognitive, language, and motor development of three-year-old children were calculated and validated. The geometric mean of the total mercury concentration in meconium was 89.6 ng g(-1). The methylmercury concentrations in hair, fingernail, and toenail samples were 1.96, 0.64, and 0.55 μg g(-1), respectively. Seventy percent of children had hair methylmercury concentrations exceeding the U.S. environmental protection agency (EPA) reference of 1 μg g(-1). A significantly positive correlation was obtained between methylmercury levels in hair, fingernail, and toenail. These methylmercury levels were also significantly positively correlated with the childrens fish intake and negatively correlated with a Bayley-III scale score of expressive language. The prenatal mercury exposure, however, did not show significant influence on neurological development. High fish consumption appears to be a critical risk factor for methylmercury levels in children and may cause a lower expressive language score.

Mercury concentration in meconium and risk assessment of fish consumption among pregnant women in Taiwan.

Meconium is a matrix that can be obtained easily and noninvasively and is useful for detecting antenatal fetal exposure to environmental toxins. Taiwan is an island with high fish consumption, and many pregnant women would like to enjoy the benefits of fish without jeopardizing their health or that of their child. The aim of this study is to assess the mercury concentration in meconium in relation to the health risk of mercury exposure. A total of 198 mother-infant pairs residing in the city of HsinChu were recruited for the study between January 2007 and June 2007. The average mean concentration of mercury in meconium was 79.2+/-7.3 ng g(-1) dry wt We use the Monte Carlo technique to assess the uncertainty in risk assessment and the impact of these uncertainties on the estimation of expected risk of mercury intake from fish in mothers. Based on the FAO/WHOs tolerable daily intake of methylmercury (0.23 microg kg(-1)d(-1)), we found that 17.3% and 14.0% of the daily mercury exposure estimated exceeded the reference dose for foreign-born and Taiwan-born mothers, respectively. We found that the mercury concentration in meconium was much higher than in other studies, except for one study done in Tagum in the Philippines where mercury is used in gold mining. This may be because Asia is the largest emitter of anthropogenic mercury, accounting for 53% of worldwide emissions. Sensitivity analysis suggests that mercury concentration in fish and the rate of ingesting fish may be the key parameters for governments offering risk management guidance to protect the health of mothers and unborn babies.

Increased risk of attention-deficit/hyperactivity disorder associated with exposure to organophosphate pesticide in Taiwanese children

Attention‐deficit/hyperactivity disorder (ADHD) is male predominated, and the etiology of this disorder remains unclear. Past studies have assessed the association of low‐level organophosphate pesticide exposure with childhood ADHD cross‐sectionally and prospectively. However, the results have been inconsistent. A first case–control study was performed to investigate the relationship between organophosphate pesticide exposure and ADHD with adjusted covariates. We recruited 97 doctor‐diagnosed ADHD cases and 110 non‐ADHD controls who were 4–15 years of age. Exposure was assessed using urinary levels of dialkylphosphate metabolites, which are biomarkers of OP pesticide exposure. Blood lead levels and polymorphisms of two commonly verified dopaminergic‐related genes (the D4 dopamine receptor gene DRD4 and the dopamine transporter gene DAT1) were also analyzed. The sociodemographics and lifestyles of the children and of the mothers during pregnancy were collected using a questionnaire. The blood lead levels of both groups were similar (1.57 ± 0.73 vs. 1.73 ± 0.77 μg/dL, p = 0.15). Significant urinary concentration differences in one of the six dialkylphosphate metabolites, dimethylphosphate (DMP), were found between ADHD and control subjects (322.92 ± 315.68 vs. 224.37 ± 156.58 nmol/g cr., p < 0.01). A dose–response relationship was found between urinary concentrations of DMP and ADHD in both crude and adjusted analyses (p for trend<0.05). Children with higher urinary DMP concentrations may have a twofold to threefold increased risk of being diagnosed with ADHD. We report a dose–response relationship between child DMP levels and ADHD. Organophosphate pesticide exposure may have deleterious effects on childrens neurodevelopment, particularly the development of ADHD.

Mouthing activity data for children aged 7 to 35 months in Taiwan

Young children’s mouthing activities thought to be among the most important exposure pathways. Unfortunately, mouthing activity studies have only been conducted in a few countries. In the current study, we used videotaping and computer-based translating method to obtain mouthing activity data for 66 children aged 7–35 months in Taiwan. The median indoor hand-to-mouth and object-to-mouth frequencies were 8.91 and 11.39 contacts/h, respectively. The median indoor hand-to-mouth and object-to-mouth hourly contact durations were 0.34 and 0.46 min/h, respectively. The indoor object-to-mouth activities were significantly and negatively correlated with age. Children aged 12 to <24 months in the current study had lower indoor hand-to-mouth and object-to-mouth frequencies than children of same age group in the United States. We also found that indoor mouthing duration with pacifier was significantly and negatively correlated with indoor mouthing duration with other non-dietary objects. The results of the current study indicate that the mouthing behaviors may be different between different countries or populations with different ethnic or lifestyle characteristics. We conclude that using hand-to-mouth frequency values from the current literature may not be most reliable for estimating non-dietary exposures of young children living in Taiwan or even in other similar Asian countries.

Fetal exposure to environmental neurotoxins in Taiwan

Mercury (Hg), lead (Pb), cadmium (Cd), and arsenic (As) are recognized neurotoxins in children that particularly affect neurodevelopment and intellectual performance. Based on the hypothesis that the fetal basis of adult disease is fetal toxic exposure that results in adverse outcomes in adulthood, we explored the concentrations of key neurotoxins (i.e., Hg, Pb, Cd, and As) in meconium to identify the risk factors associated with these concentrations. From January 2007 to December 2009, 545 mother-infant pairs were recruited. The geometric mean concentrations of Pb and As in the meconium of babies of foreign-born mothers (22.9 and 38.1 µg/kg dry weight, respectively) were significantly greater than those of babies of Taiwan-born mothers (17.5 and 33.0 µg/kg dry weight, respectively). Maternal age (≥30 y), maternal education, use of traditional Chinese herbs during pregnancy, and fish cutlet consumption (≥3 meals/wk) were risk factors associated with concentrations of key prenatal neurotoxins. The Taiwan government should focus more attention on providing intervention programs for immigrant mothers to help protect the health of unborn babies. Further investigation on how multiple neurotoxins influence prenatal neurodevelopment is warranted.

Soil ingestion rates for children under 3 years old in Taiwan.

Soil and dust ingestion rates by children are among the most critical exposure factors in determining risks to children from exposures to environmental contaminants in soil and dust. We believe this is the first published soil ingestion study for children in Taiwan using tracer element methodology. In this study, 66 children under 3 years of age were enrolled from Taiwan. Three days of fecal samples and a 24-h duplicate food sample were collected. The soil and household dust samples were also collected from children’s homes. Soil ingestion rates were estimated based on silicon (Si) and titanium (Ti). The average soil ingestion rates were 9.6±19.2 mg/day based on Si as a tracer. The estimated soil ingestion rates based on Si did not have statistically significant differences by children’s age and gender, although the average soil ingestion rates clearly increased as a function of children’s age category. The estimated soil ingestion rates based on Si was significantly and positively correlated with the sum of indoor and outdoor hand-to-mouth frequency rates. The average soil ingestion rates based on Si were generally lower than the results from previous studies for the US children. Ti may not be a suitable tracer for estimating soil ingestion rates in Taiwan because the Ti dioxide is a common additive in food. To the best of our knowledge, this is the first study that investigated the correlations between soil ingestion rates and mouthing behaviors in Taiwan or other parts of Asia. It is also the first study that could compare available soil ingestion data from different countries and/or different cultures. The hand-to-mouth frequency and health habits are important to estimate the soil ingestion exposure for children. The results in this study are particularly important when assessing children’s exposure and potential health risk from nearby contaminated soils in Taiwan.

Methylmercury Concentration in Fish and Risk-Benefit Assessment of Fish Intake among Pregnant versus Infertile Women in Taiwan.

This study examined methylmercury (MeHg) concentrations in fish, the daily MeHg exposure dose, and the risk–benefit of MeHg, ω-3 polyunsaturated fatty acid (ω-3 PUFA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) related to fish intake among pregnant and infertile women in Taiwan. The measured MeHg concentrations in fish did not exceed the Codex guideline level of 1 mg/kg. Swordfish (0.28 ± 0.23 mg/kg) and tuna (0.14 ± 0.13 mg/kg) had the highest MeHg concentrations. The MeHg concentration in the hair of infertile women (1.82 ± 0.14 mg/kg) was significantly greater than that of pregnant women (1.24 ± 0.18 mg/kg). In addition, 80% of infertile women and 68% of pregnant women had MeHg concentrations in hair that exceeded the USEPA reference dose (1 mg/kg). The MeHg concentrations in hair were significantly and positively correlated with the estimated daily MeHg exposure dose. Based on the risk–benefit evaluation results, this paper recommends consumption of fish species with a low MeHg concentration and high concentrations of DHA + EPA and ω-3 PUFA (e.g., salmon, mackerel, and greater amberjack).

Sugar-Sweetened Beverage Consumption Is Adversely Associated with Childhood Attention Deficit/Hyperactivity Disorder.

Attention deficit/hyperactivity disorder (ADHD) is one of the most common childhood neurobehavioral conditions. Evidence of the negative effects of sugar-sweetened beverages (SSBs) on mental health has not been convincing, although a few studies have found an association between high SSB levels and attention problems in children. This study aimed to test the hypothesis that SSB consumption is associated with ADHD among children. Doctor-diagnosed ADHD cases (n = 173) and non-ADHD controls (n = 159) between age 4 to 15 were recruited. SSB consumption, socio-demographic and lifestyle characteristics of the children, as well as of their mothers’ characteristics during pregnancy, were collected using a questionnaire. Blood lead levels and polymorphisms of two commonly verified dopaminergic-related genes (the D4 dopamine receptor gene DRD4 and the dopamine transporter gene DAT1) were also analyzed. There was a dose-response relationship between SSB consumption and ADHD. After covariates were adjusted, children who consumed SSBs at moderate levels and high levels had 1.36 and 3.69 odds, respectively, of having ADHD, compared with those who did not consume SSBs (p for trend < 0.05). Similar results were obtained when females were excluded. Our findings highlighted the adverse correlation between SSB consumption and ADHD and indicated a dose-response effect even after covariates were adjusted.

Attention Deficit/Hyperactivity Disorder and Urinary Nonylphenol Levels: A Case-Control Study in Taiwanese Children

Objective Nonylphenol (NP) belongs to the family of endocrine disruptors, and it is widely used in industrial applications and is ubiquitous in daily foods. Animal studies have suggested that NP exposure might promote motor hyperactivity, likely by causing deficits in dopaminergic neurons. However, research assessing NP exposure and epidemiology studies on human populations are limited. The aim of this study was to explore the association between child NP exposure and ADHD while considering particular covariants, such as lead levels and dopamine-related gene variations. Methods A case-control study was conducted on patients with clinically diagnosed ADHD; the Swanson, Nolan and Pelham, Fourth Revision (SNAP-IV) questionnaire was used to identify normal controls aged 4–15 years. Participants were examined for urinary NP concentrations, blood lead levels, and select single-nucleotide polymorphisms of two dopamine-related genes (D4 dopamine receptor, DRD4, and dopamine transporter, DAT1). Socio-demographic variables, maternal lifestyle factors during pregnancy and family medical history were obtained using a questionnaire. Results A total of 97 children with doctor-diagnosed ADHD and 110 normal controls were enrolled. The blood lead levels in both groups were similar (1.57±0.73 vs. 1.73±0.77 μg/dL, p = 0.15). No significant difference in urinary NP concentration was found between the children with ADHD and the control subjects (4.52±3.22 μg/g cr. vs. 4.64±2.95 μg/g cr., p = 0.43). ADHD was significantly more prevalent among males in this study (male to female ratio: 5:1 for the ADHD group and 1.3:1 for the control group, p<0.01). The analysis was repeated after excluding the females, but this had no effect on the association between NP and ADHD. The regression model, including or excluding females, indicated no increased odds of having ADHD in the context of NP exposure after adjusting for covariants. Conclusion This study indicated that NP exposure might not promote ADHD in children, even though children in Taiwan had relatively high levels of NP compared to those reported previously and those in developed nations.

Preliminary study of blood methylmercury effects on reproductive hormones and relevant factors among infertile and pregnant women in Taiwan

Methylmercury (MeHg) is the most poisonous mercury species and an endocrine-disrupting chemical that could cause reproductive and developmental harm effects in animals. In this study, we recruited 310 infertile women and 57 pregnant women and investigated their blood MeHg levels. The distribution of blood reproductive hormone, selenium and zinc levels, and the difference of relevant factors by the reference level of blood MeHg (5.8 μg/L) of infertile women were further examined. Results showed that greater percentages of sashimi consumption, frequencies of Chinese herbal medicine use, alcohol consumption, and lack of physical activity were observed in infertile women than those for pregnant women. Blood MeHg concentration was significantly greater in infertile than that in pregnant women. Significant concentration differences for FSH and LH by the dichotomized reference level of blood MeHg (5.8 μg/L) in infertile women were not observed, which may stem from that these reproductive hormones in participated infertile women were mostly in the normal reference range. Consumption of fish and sashimi represented the major source of MeHg exposure in infertile women. MeHg levels were elevated in infertile women, and consistent with fish consumption frequency. Compared to the referent level of blood MeHg levels <5.8 μg/L, the elevated blood MeHg levels (⩾5.8 μg/L) in infertile women were 3.35 and 4.42 folds risk in categorized frequencies of fish consumption 1-2 meals per week and more than 3 meals per week, respectively. The obtained results provide evidences and help updating the advisory of fish consumption and improving womens reproductive health.