Chia-Huang Chang

Neonatal outcomes of intrauterine nonylphenol exposure—A longitudinal cohort study in Taiwan

BACKGROUND Nonylphenol (NP) is an environmental hormone with proven estrogenic effects. Although its adverse effects on animals are well documented, the effects of NP exposure on humans remain unclear, and those on the human foetus are completely unknown. This study explores the effects of intrauterine NP exposure on neonates. METHODS A cohort of pregnant women was established in a medical centre in northern Taiwan. Urine samples from the first, second, and third trimesters of gestation were collected. Urinary NP concentration was measured by high-performance liquid chromatography coupled with fluorescent detection. Neonatal outcomes were evaluated immediately after delivery. A mixed-effects model using a generalised estimating equation was applied to assess the association between gestational age, maternal body weight, and maternal NP concentration throughout the three trimesters. A multivariable regression model was used to determine the association between maternal NP level in urine in each trimester and neonatal outcomes. RESULTS In total, 162 singleton pregnant women completed this study through delivery. The geometric mean of creatinine-adjusted urinary NP concentrations were 4.27 μg/g, 4.21 μg/g, and 4.10 μg/g in the first, second, and third trimesters, respectively. Pregnant women whose urinary NP concentrations were above the median in the second trimester had low maternal weight gain (β=-1.55 kg, p=0.02) and short neonatal body length (β=-0.47 cm, p=0.04). Women with an above-median urinary NP concentration had an odds ratio of having a small for gestational age (SGA) neonate of 7.81 (p<0.05). CONCLUSIONS This study indicates that maternal high NP exposure in the second trimester is associated with SGA, decreased foetal body length at birth, and low maternal weight gain. The effects of this endocrine-disrupting substance on pregnant women and foetuses should be a concern during gestation.

The association between maternal nonylphenol exposure and parity on neonatal birth weight: A cohort study in Taiwan

BACKGROUND The aim of this study was to explore the association between NP exposure and parity and their effect on neonatal birth weight. METHODS A cohort of pregnant women was established in a medical center in North Taiwan. Urinary NP concentration was determined by high-performance liquid chromatography coupled with fluorescent detection and adjusted using creatinine. A multivariable regression model was fit to determine the association between the maternal NP level in each trimester and neonatal birth weight. The odds ratios (ORs) of infant birth weight below the 10th, 25th, and 50th percentiles, comparing pregnant women with the different NP exposure levels, was estimated using a logistic regression. RESULTS Of the 162 pregnant women in the study, 99 were multiparas and 63 were primiparas. After adjusting for other covariates, the NP level in the second trimester had a significant association with birth weight in the primiparas (β = -182.49 g, p value = 0.02). The OR of low infant birth weight, comparing pregnant women with different NP levels, was increased by decreasing the cutoff percentile for birth weight (OR = 1.18 for the 50th percentile, 2.12 for the 25th percentile, and 7.81 for the 10th percentile). The odds of primiparas with high NP level having a low neonatal birth weight increased to 3.87, 11.77, and 9.40 for the three different percentiles (p value < 0.05). CONCLUSION Maternal NP exposure level is associated with an increased risk of low neonatal weight. Primiparas are especially at risk, and the second trimester of pregnancy may be the critical stage of exposure.

Dark-Recovery Experiences, Coping Strategies, and Needs of Adult Heart Transplant Recipients in Taiwan

AIMS The aim of this project was to identify the dark-recovery experiences (DRE) that adult heart transplant recipients (AHTRs) perceived as causing the most suffering after heart transplantation (HT). In artition, we sought to explore the stage-specific difficulties, coping strategies, and helpers for transplant recipients DRE in Taiwan. METHODS A qualitative design was employed using a sample group of patients with DRE. Retrospective data collected by face-to-face in-depth interviews were subjected to content analysis. RESULTS A total of 20 AHTRs (16 men, 4 women) participated in this research. Their ages ranged from 32-70 years (mean, 46.95 years). Their post-HT timeframe ranged from 3 months-2.10 years. The subjects reported DRE the across preoperative intensive care unit (ICU), postoperative floor unit, and even after the hospital discharge stages. Four major difficulties during DRE were reported: (1) becoming a burden for families (all stages); (2) unfamiliar with medical protocols, environment, and policy (ICU stage); (3) mental and physical discomforts caused by the invasive examinations and unstable health condition (post-ICU to postdischarge stages); and (4) sense of uncertainty about health progression and quality of life in the future (post-ICU to postdischarge stages). Four coping strategies were used for DRE: (1) asking religious support (all stages); (2) changing mindsets and taking positive attitudes to live with difficulties (ICU to postdischarge stages); (3) setting goals for health maintenance and recovery (post-ICU to postdischarge stages); and (4) planning to look for an appropriate job in the future (postdischarge stages). Families and religious persons were cited as helpers (all stages), as well as health professionals (ICU to postdischarge stages), other AHTRs (post-ICU to postdischarge stages), and the social welfare systems (postdischarge stages). CONCLUSION DRE, coping strategies, and related helpers in Taiwan were systematically explored in this project. With this information, the transplantation team will be empowered to provide better care for AHTRs during their most vulnerable time.

Concurrent exposures to nonylphenol, bisphenol A, phthalates, and organophosphate pesticides on birth outcomes: A cohort study in Taipei, Taiwan

Prenatal exposure to phenols, phthalates (PAEs), and organophosphate (OP) pesticides may increase the risk of abnormal birth outcomes. However, many previous studies have examined exposure to a limited number of chemical classes or exposure profiles limited to a specific stage of pregnancy. This study aims to characterize the concurrent exposure scenario throughout pregnancy by simultaneously monitoring internal doses of several endocrine-disrupting compounds (EDCs), including 2 phenols (nonylphenol (NP) and bisphenol A (BPA)), 9 PAEs, and 6 OP pesticide metabolites and to assess the relationships between concurrent exposure to EDCs and infant birth weight, length, and head and chest circumference. One hundred and sixty two women provided three spot urine samples at approximately 11 and 26weeks gestation and at delivery. We applied multivariable linear regression and ridge regression models to estimate the effects of separate and correlated exposures. Multivariable linear regression models revealed that women with short birth-length infants had significantly higher urinary second-trimester NP levels (50th percentile, 5.03μg/g creatinine) (β=-0.47cm; 95% CI=-0.93 to -0.01). Similarly significant relationships were observed between second-trimester mono-methyl phthalate (MMP) exposure and short birth length, second-trimester ΣPAEs and short birth length, second-trimester ΣPAEs exposure and reduced head and chest circumference, second-trimester diethylphosphate (DEP) exposure and reduced birth weight and length, and second-trimester ΣDEPs exposure and short birth length. Women with urinary BPA above the 75th percentile or ΣPAEs levels above the 50th percentile in the third trimester had infants with significantly reduced head circumference. These observations suggest that the second trimester may be the critical stage of susceptibility for fetal development. In ridge regression models, for which women with fewer measures for exposure to NP, BPA, MMP, ΣPAEs, DEP and ΣDEPs simultaneously were available, no relationships were found with infant size at birth. Additional studies with larger sample sizes are warranted.

The critical fetal stage for maternal manganese exposure

Prenatal exposure and the health effects of that exposure have been intensively studied for a variety of environmental pollutants and trace elements. However, few studies have compared susceptibilities among the three trimesters of gestation. Manganese (Mn) is a naturally occurring and abundant trace element in the environment. Although the effects of Mn on animals are well documented, knowledge of the effects of Mn exposure on pregnant women and fetuses remains limited. A longitudinal study was conducted by collecting blood samples during all three trimesters, and Mn exposure was completely characterized during gestation. The aims of this study were to examine the effects of maternal Mn exposure on neonatal birth outcomes and to explore the critical stage of these effects. In total, 38, 76 and 76 samples were obtained from singleton pregnant women in their first, second and third trimesters, respectively. The cohort of pregnant women was selected at a medical center in northern Taiwan. Erythrocyte samples were collected during the first, second and third trimesters of gestation. Erythrocyte Mn concentrations were measured by inductively coupled plasma mass spectrometry. Neonatal birth outcomes were evaluated immediately after delivery. A multivariate regression model was used to determine the associations between maternal Mn levels in erythrocytes in each trimester and neonatal birth outcomes. The geometric mean concentrations of Mn were 2.93 μg/dL, 3.96 μg/dL and 4.41 μg/dL in the first, second and third trimesters, respectively. After adjusting for potential confounders, a consistently negative association was found between maternal Mn levels throughout the three trimesters and birth outcomes. Log-transformed Mn levels in maternal erythrocytes in the second trimester were significantly associated with neonatal birth weight, head and chest circumferences, respectively (β=-556.98 g, p=0.038; β=-1.87 cm, p=0.045; β=-2.74 cm, p=0.024). Despite the limited sample size in the first trimester, negative effects of maternal Mn levels on birth weight (β=-1108.95 g, p<0.01) and chest circumference (β=-4.40 cm, p=0.019) were also observed.

Perceived Health-Related Quality of Life in Heart Transplant Recipients With vs Without Preoperative ECMO in Taiwan: Between-Method Triangulation Study

OBJECTIVE To compare changes in overall health-related quality of life (HRQoL), working competence, and physical functions in heart transplant (HTx) recipients with vs without preoperative extracorporeal membrane oxygenation (ECMO) at 3 crucial stages post-HTx: 1 and 6 months and 1 year. PATIENTS AND METHODS This between-method triangulation study included qualitative and quantitative data for patients recruited from a medical center with 2200 beds. Quantitative data were obtained using a vertical visual analog scale and the Taiwan version of the World Health Organization Quality of Life Questionnaire. Six semistructured qualitative questions were added to further explore factors that influence changes in Social domains of HRQoL between the 4 groups across recovery stages. RESULTS The 50 patients (86% men and 14% women) ranged in age from 20 to 70 years (mean age, 47.68 years). Time post-HTx ranged from 1 year to 4 years and 1 month, and 16% had received preoperative ECMO therapy. Mean (SD) HRQoL, working competence, and physical functions improved from 54.76 (24.44), 31.8 (26.53), and 80.00 (33.67), respectively, at 1 month post-HTx (r=.48) to 65.76 (20.24), 50.90 (25.23), and 96.80 (11.05) at 6 months (r=.52) and 74.40 (13.65), 64.30 (21.48), and 98.8 (7.80) at 12 months (r=.44), with moderately significant differences. Compared with the non-ECMO group, the preoperative ECMO group perceived lower (stage 1), similar (stage 2), and higher (stage 3) working competence. Thirty-two percent of recipients resumed stable jobs across the 3 stages (10%, 8%, and 14%, respectively), and reported higher working competence and physical functions compared with other patients (68%) (P<.001). Recipients with stable marriages (P=.046), higher educational achievement level (P=.004), and stable jobs (P=.001) reported greater overall HRQoL across the 3 stages. CONCLUSION Heart transplant recipients reported higher overall HRQoL, working competence, and physical functions across the 3 recovery stages during 12 months post-HTX. Three major influencing factors identified included stable marriage, higher educational achievement level, and stable job status.

The Association between Nonylphenols and Sexual Hormones Levels among Pregnant Women: A Cohort Study in Taiwan

Background Nonylphenol (NP) has been proven as an endocrine disrupter and had the ability to interfere with the endocrine system. Though the health effects of NP on pregnant women and their fetuses are sustained, these negative associations related to the mechanisms of regulation for estrogen during pregnancy need to be further clarified. The objective of this study is to explore the association between maternal NP and hormonal levels, such as estradiol, testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH), and progesterone. Methods A pregnant women cohort was established in North Taiwan between March and December 2010. Maternal urine and blood samples from the first, second, and third trimesters of gestation were collected. Urinary NP concentration was measured by high-performance liquid chromatography coupled with fluorescent detection. A mixed-effects model using a generalised estimating equation (GEE) was applied to assess the associations between maternal NP concentration and plasma hormones throughout the three trimesters. Results In total, 162 singleton pregnant women completed this study through delivery. The geometric mean of creatinine-adjusted urinary NP concentrations were 4.27, 4.21, and 4.10 µg/g cre. in the first, second, and third trimesters respectively. A natural log-transformation of urinary NP concentrations were significantly associated with LH in the GEE model (β = −0.23 mIU/ml, p<0.01). Conclusion This perspective cohort study demonstrates that negative association occurs between maternal NP exposure and plasma LH levels. The estrogen-mimic effect of NP might influence the negative feedback on LH during pregnancy.

Evidence of high di(2-ethylhexyl) phthalate (DEHP) exposure due to tainted food intake in Taiwanese pregnant women and the health effects on birth outcomes

The contamination of a clouding agent with di(2-ethylhexyl) phthalate (DEHP), a substitute emulsifier-containing compound used in a variety of foods was announced on May 23, 2011. The aims of this study were as follows (1) compare the urine phthalates (PAE) metabolites concentration and estimate the daily intake (DI) of PAEs in pregnant women before and after the tainted food scandal and (2) examine the effect of relatively high PAEs exposure on birth outcome. One-hundred twelve pregnant women in Northern Taiwan participated in this study from March to December 2010, i.e., before the tainted food scandal. After the tainted food scandal, we collected 69, 73, and 180 urine specimens (January 2013 to August 2014) from women whom were in their first, second, and third trimesters of pregnancy, respectively. We measure urinary DEHP metabolite concentrations to estimate the DI of DEHP and the hazard quotient (HQ) of subjects. This was the first study to assess the effects of DEHP-tainted food scandal exposure in pregnant women across the three trimesters of pregnancy. After the tainted food report, the concentrations of urine PAE metabolite were significantly decreased, especially those of DEHP metabolites. Based on different reference limit values, the percentages of pregnant women whose HQDEHP value exceeded the limit ranged from 0.53% to 8.93%. Despite this low frequency, the higher ΣPAE exposure during the second trimester may significantly increase the risk of relatively low birth height compared to the lower exposure group (β=-0.63 (-1.20 to -0.06)). Our results support the hypothesis that exposure to relatively high concentrations of DEHP in pregnant Taiwanese women may have an adverse effect on birth outcomes. The percentage of subjects whose exposure level exceeded the exposure limit was low; however, high PAEs exposure appears to be significantly associated with birth outcomes. Therefore, we suggest that reference dose for PAEs should be revised.

The interactions among organophosphate pesticide exposure, oxidative stress, and genetic polymorphisms of dopamine receptor D4 increase the risk of attention deficit/hyperactivity disorder in children

Objective The aim of this study was to clarify the association between organophosphate pesticides (OPs) and attention‐deficit/hyperactivity disorder (ADHD) related to oxidative stress and genetic polymorphisms. Methods This case‐control study enrolled 93 children with ADHD and 112 control children in north Taiwan. Six dialkyl phosphate (DAP) metabolites of OPs and oxidative stress biomarkers were analyzed. Polymorphisms of the dopamine receptor D4 gene (DRD4) were identified. Results Children with ADHD had significantly higher dimethylphosphate (DMP, 236.69 nmol/g cre. vs. 186.84 nmol/g cre., p value = 0.01) and 4‐hydroxy‐2‐nonenal‐mercapturic acid (HNE‐MA, 28.95 &mgr;g/g cre. vs. 16.55 &mgr;g/g cre., p value<0.01) concentrations than control children. Children who carried DRD4 GA/AA genotypes (rs752306) were less likely than those who carried the DRD4 GG genotype to have ADHD (odds ratio [OR]: 0.45, 95% CI: 0.24–0.84). The estimated value of the AP (attributable proportion due to interaction) was 0.59 (95% CI: 0.13–1.05), indicating that 59% of ADHD cases in DMP‐exposed children with the DRD4 GG genotype were due to the gene‐environment interaction. After adjustment for other covariates, children who carried the DRD4 GG genotype, had been exposed to high DMP levels (more than the median), and had high HNE‐MA levels had a significantly increased risk for developing ADHD (OR = 11.74, 95% CI: 2.12–65.04). Conclusion This study indicated a gene‐environment interaction in the risk of ADHD in children. The association between DMP and ADHD in children might relate to the mechanism of lipid peroxidation. Dose‐response relationships and the combined effects of OPs, oxidative stress, and genetic polymorphism on ADHD should not be neglected. HighlightsChildren with ADHD had high dimethylphosphate (DMP) and lipid peroxidation levels.An additive interaction between DRD4 polymorphism and DMP levels for ADHD existed.The combined effects of DRD4, DMP, and HNE‐MA increased the risk of developing ADHD.

Do the Levels of Maternal Plasma Trace Elements Affect Fetal Nuchal Translucency Thickness

Objective Fetal nuchal translucency (NT) thickness is an important marker for prenatal screening; however, studies focusing on the correlation between maternal trace element levels and NT thickness are limited. The aim of this study was to evaluate maternal trace element levels during the first trimester and to investigate the association between maternal trace element levels and fetal NT thickness. Methods In total, 113 samples were obtained from singleton pregnant women. Maternal plasma samples were collected in the first trimester of gestation. Plasma trace element levels were measured using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Nuchal translucency thickness was measured using ultrasonography at 10–14 weeks of gestation. Results We found that maternal plasma potassium (K) levels had a significant negative correlation with both NT (r = -0.230, p < 0.05) and NT Multiples of the Median (NT MoM) (r = -0.206, p < 0.05). After adjustment for potential confounders, log-transformed maternal plasma potassium levels in the first trimester were significantly associated with fetal NT (NT MoM: β = -0.68, p < 0.05; NT: β = -1.20, p < 0.01). Although not statistically significant, the As, Hg and Pb levels in maternal plasma were positively correlated with NT, and the Mg, Cu, Zn, Na and Ca levels were negatively correlated with NT. Conclusion Maternal plasma K levels during the first trimester appeared to be associated with NT thickness. The essential elements tended to decrease NT thickness, and non-essential elements tended to increase it.