Mei-Huei Chen

Perfluorinated Compounds in Umbilical Cord Blood and Adverse Birth Outcomes

Background Previous animal studies have shown that perfluorinated compounds (PFCs) have adverse impacts on birth outcomes, but the results have been inconclusive in humans. We investigated associations between prenatal exposure to perfluorooctanoic acid (PFOA), perfluorooctyl sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUA) and birth outcomes. Methods In total, 429 mother-infant pairs were recruited from the Taiwan Birth Panel Study (TBPS). Demographic data were obtained by interviewing mothers using a structured questionnaire and birth outcomes were extracted from medical records. Cord blood was collected for PFOA, PFOS, PFNA, and PFUA analysis by ultra-high-performance liquid chromatography/tandem mass spectrometry. Results The geometric mean (standard deviation) levels of PFOA, PFOS, PFNA, and PFUA in cord blood plasma were 1.84 (2.23), 5.94 (1.95), 2.36(4.74), and 10.26 (3.07) ng/mL, respectively. Only PFOS levels were found to be inversely associated with gestational age, birth weight, and head circumference [per ln unit: adjusted β (95% confidence interval, CI) = −0.37 (−0.60, −0.13) wks, −110.2 (−176.0, −44.5) gm and −0.25 (−0.46, −0.05) cm]. Additionally, the odds ratio of preterm birth, low birth weight, and small for gestational age increased with PFOS exposure [per ln unit: adjusted odds ratio (OR) (95%CI) = 2.45 (1.47, 4.08), 2.61(0.85, 8.03) and 2.27 (1.25, 4.15)]. When PFOS levels were divided into quartiles, a dose-response relation was observed. However, PFOA, PFNA, and PFUA were not observed to have any convincing impact on birth outcomes. Conclusions An adverse dose-dependent association was observed between prenatal PFOS exposure and birth outcomes. However, no associations were found for the other examined PFCs.

Perfluorinated compound levels in cord blood and neurodevelopment at 2 years of age.

Background: Epidemiologic data regarding the potential neurotoxicity of perfluorinated compounds (PFCs) are inconclusive. We investigated the associations between in utero exposure to perfluorooctanoic acid (PFOA) and perfluorooctyl sulfonate (PFOS) and early childhood neurodevelopment. Methods: We recruited 239 mother–infant pairs in northern Taiwan from the Taiwan Birth Panel Study, which was established in 2004. We examined the association between PFCs in cord blood and children’s neurodevelopment at 2 years of age, using the Comprehensive Developmental Inventory for Infants and Toddlers. This tool contains cognitive, language, motor, social, and self-help domains; test scores were further transformed into developmental quotients according to standardized norms. All multivariate regression models were adjusted for infant sex and gestational age, maternal education, family income, cord blood cotinine levels, postnatal environmental tobacco smoke exposure, and breastfeeding. Results: Prenatal PFOS concentrations in both untransformed and natural log (Ln)-transformed values were associated with adverse performance on the whole test and the domains related to development. A dose–response relationship was observed when PFOS levels were categorized into four groups. This association was most obvious in relation to the gross-motor subdomain. Across the PFOS interquartile range, the quotients of the gross-motor subdomain decreased by 3.7 points (95% confidence interval [CI] = −6.0 to −1.5), with an increasing odds ratio of poor performance (2.4; 95% CI = 1.3 to 4.2). In contrast, measures of association between PFOA concentrations and test scores were close to null. Conclusions: Prenatal exposure to PFOS, but not PFOA, may affect children’s development, especially gross-motor development at 2 years of age.

High perinatal seroprevalence of cytomegalovirus in northern Taiwan

Aim:  The living style, health‐care system and socio‐economic environments have changed substantially in Taiwan over past 20 years. This study was aimed to estimate the current perinatal cytomegalovirus (CMV) seroprevalence in northern Taiwan.

Pulse pressure, aortic regurgitation and carotid atherosclerosis: a comparison between hypertensives and normotensives

Pulse pressure (PP) has often been associated with cardiovascular morbidity and mortality. Patients with aortic regurgitation (AR) often have increased PP. The aim of this study is to investigate the associations among PP, AR and extracranial carotid artery (ECCA) carotid atherosclerosis (CA) in hypertensives and age‐ and sex‐matched normotensives. Two hundred and sixty‐three hypertensive patients and 270 normotensive subjects from the Chin‐Shan Community Cardiovascular Cohort participated in this study in 1996. CA, expressed as maximal common carotid artery intima‐media thickness (IMT) ≥75th percentile and ECCA plaque score >6, was measured using high‐resolution B‐mode ultrasonography. The presence of AR was assessed by echocardiography, and their relationships with CA were evaluated. Results showed measurements of CA significantly associated with increased PP. Presence of AR associated with CA, but this relationship was attenuated after controlling for age. Multivariate logistic regression analyses revealed that an ECCA score >6 significantly increase the risk in conjunction with PP, age and smoking in hypertensives. Correspondingly, CA increased with age, smoking and left ventricular hypertrophy on electrocardiography but not PP in normotensives. In conclusion, higher PP is strongly associated with CA in patients with hypertension. In terms of risk stratification, PP is more important in hypertensives than in normotensives which seem to imply that pulsatile haemodynamic component of BP is crucial in association with atherosclerosis.

Neonatal–maternal factors and perfluoroalkyl substances in cord blood

Perfluoroalkyl substances (PFASs) can cross the placenta, enter fetal circulation, and were found to correlate with adverse fetal growth. However, determinants of cord blood PFASs are not fully characterized. The study aimed to explore the association between PFASs and neonatal-maternal factors within a Taiwanese birth cohort. We selected subjects from Taiwan Birth Panel Study, which enrolled 486 infant-mother pairs in 2004-2005. We collected cord blood and analyzed perfluorooctanoic acid (PFOA), perfluorooctanyl sulfonate (PFOS), perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUA) using a simple protein precipitation and an ultra-high performance liquid chromatography/tandem mass spectrometry. We retrieved information pertaining to maternal socio-demographics, lifestyle- and dietary-related factors through structured questionnaires during the postpartum hospital stay. A total of 439 subjects, with 90% response rate, have completed serum analysis and questionnaire survey. The median concentrations for PFOA, PFOS, PFNA, and PFUA in cord blood were 1.86, 5.67, 3.00, and 13.5ngmL(-1), respectively. After adjusting for potential confounders, multiple linear regression models revealed that log10-PFOA was positively associated with maternal age (β=0.011) and negatively associated with multiparity (β=-0.044). Log10-PFOS was negatively correlated with birth weight (β=-0.011) and higher maternal education (senior high school: β=-0.067; university: β=-0.088). Log10-PFUA tended to negatively associate with gender, male infants (β=-0.075), and using cosmetics during pregnancy (β=-0.065). Interestingly, presence of cockroaches in the home was positively associated with log10-PFOA (β=0.041) and 1og10-PFNA (β=0.123). In conclusion, this study demonstrated several factors to correlate with cord blood PFASs and further investigation are still needed for confirmation of exposure routes.

Effect of rotating shift work on childbearing and birth weight: a study of women working in a semiconductor manufacturing factory

BackgroundStable circadian rhythm is important for both maternal and fetal health. This retrospective analysis of women in a semiconductor factory evaluated the effect of shift work exposure on childbearing and birth weight.MethodsRecords of 440 female employees (initial mean age: 28.4 years) including 111 mothers who had 158 live births during the period of observation (1997–2007) were reviewed. The data analyzed included maternal age, general health condition, highest educational level, life-style and occupational factors, as well as newborn gender, birth weight, birth order and gestational age.ResultsThe childbearing rates of female workers on three different work schedules (consistent daytime work (CDW), intermittent (i-) or persistent (p-) rotating shift works (RSW)) were 32.1%, 20.0% and 25.4%, respectively (P=0.047). After controlling for potential confounding factors, childbearing rates among women with CDW exceeded those of shift workers (odds ratio (OR), 1.7; 95% confidence interval (CI), 1.0–3.0). The birth weights of newborns from mothers on the three work schedules (CDW, i-RSW and p-RSW) were significantly different (3271.7±395.4, 3251.3±460.9, and 2998.5±381.2 g, respectively (P<0.01). Newborns within the lightest birth weight quintile were significantly more likely to be born to mothers with exposure to p-RSW (OR, 4.3; 95% CI, 1.1–16.8).ConclusionsRotating shift work exposure was significantly associated with decreased childbearing and lighter birth weight in women working in this semiconductor manufacturing factory. Work schedules should be carefully planned for female employees who are pregnant or preparing for pregnancy. Prenatal evaluations for mothers with persistent day-night rotating shift work exposures are especially necessary.

Perfluoroalkyl substances in cord blood and attention deficit/hyperactivity disorder symptoms in seven-year-old children.

OBJECTIVE The effect of perfluoroalkyl substances (PFASs) on the development of neurotoxicity in children is still controversial. This study aimed to evaluate the association between in utero exposure to four PFASs and the development of neurobehavioral symptoms related to attention deficit hyperactivity disorder (ADHD) in early childhood. METHODS Eligible study subjects were selected from the Taiwan Birth Panel Study and the Taiwan Early-Life Cohort, which enrolled a total of 1526 mother-infant pairs during 2004 and 2005. We collected umbilical cord blood and analyzed perfluorooctanoic acid (PFOA), perfluorooctanyl sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUA) levels. When a child was 7 years old, to evaluate ADHD related neurobehavioral symptoms, their parents completed the Swanson, Nolan, and Pelham IV scale (SNAP-IV), the Child Behavior Checklist (CBCL), and the Strengths and Difficulties Questionnaire (SDQ) questionnaires. We used linear regression models with inverse probability weighting to explore the association between prenatal exposure to four PFASs and ADHD rating scores. RESULTS A total of 282 subjects have completed the PFASs analysis and questionnaire survey. After adjusted for potential confounders, we observed that PFNA is inversely associated with inattention and oppositional defiant disorder of SNAP-IV, and hyperactivity/inattention of SDQ. No association between PFOA, PFOS, or PFUA and ADHD symptoms was found. CONCLUSIONS Prenatal exposure to PFNA was found to associate with neurobehavioral symptoms related to ADHD among Asian seven-year-old children. Further studies are needed to elucidate the causal relationship.

Association between perfluoroalkyl substances and reproductive hormones in adolescents and young adults.

BACKGROUND Few studies have explored the association between perfluoroalkyl substances (PFAS) and reproductive hormones in adolescents and young adults. OBJECTIVES This study aimed to investigate the association of PFAS with reproductive hormones in adolescents and young adults. METHODS We recruited 540 subjects aged 12-30 years from a 1992 to 2000 mass urine screening population and established a cohort from 2006 to 2008 via invitations by mail or/and telephone. Serum PFAS levels were analyzed with a Waters ACQUITY UPLC system coupled with a Waters Quattro Premier XE triple quadrupole mass spectrometer. Serum reproductive hormone levels were measured by immunoluminometric assay with an Architect random access assay system. PFAS levels were divided into different percentiles according to their detection limits in the multiple regression models to analyze associations between reproductive hormone levels and exposure with PFAS. RESULTS The adjusted mean serum level of sex hormone-binding globulin (SHBG) decreased significantly in association with the <50th, 50-75, 75-90 and >90th percentile categories of perfluorooctanoic acid (PFOA) compared with a reference category for the females in the 12-17-year-old group. The follicle-stimulating hormone (FSH) levels were significantly decreased in association with the different percentile categories of perfluorooctane sulfonate (PFOS) in the male 12-17-year-old group and the different percentile categories of perfluoroundecanoic acid (PFUA) in the female 12-17-year-old group. The serum FSH levels in the females aged 12-17 were also decreased in association with the different percentile categories of PFUA. On the other hand, there was a significantly negative association between the different percentile categories of PFOS and the serum testosterone level among the female 12-17-year-old group. CONCLUSIONS We found that the serum concentrations of PFOA, PFOS, and PFUA were negatively associated with the serum levels of SHBG, FSH, and testosterone in the young Taiwanese population and that these effects were the strongest in the females aged 12-17. Further studies are needed to determine whether these associations are causal.

Effects of Gender on the Association of Urinary Phthalate Metabolites with Thyroid Hormones in Children: A Prospective Cohort Study in Taiwan.

Phthalates are considered endocrine disruptors. Our study assessed the gender-specific effects of phthalate exposure on thyroid function in children. In total, 189 Taiwanese children were enrolled in the study. One-spot urine and blood samples were collected for analyzing 12 phthalate metabolites in urine and thyroid hormones. The association between urinary phthalate metabolites and serum thyroid hormones was determined using a generalized linear model with a log link function; the children were categorized into groups for analysis according to the 33rd and 66th percentiles. The data were stratified according to gender and adjusted for a priori defined covariates. In girls, a positive association existed between urinary di-2-ethylhexyl phthalate (DEHP) metabolites (mono-(2-ethylhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, and mono-(2-ethyl-5-hydroxyhexyl) phthalate) and free thyroxine (T4). In boys, urinary dibutyl phthalate (DBP) metabolites (mono-i-butyl phthalate and mono-n-butyl phthalate) were positively associated with free triiodothyronine (T3). After categorizing each exposure into three groups, urinary DEHP metabolites were positively associated with free T3 levels in boys. Our results suggested that DEHP is associated with free T4 in girls and that DBP is associated with free T3 in boys. Higher DEHP metabolite concentrations exerted larger effects on free T3 in boys. These results reveal the gender-specific relationships between phthalate metabolites and thyroid hormones.

Concentration Gradient Effects of Sodium and Lithium Ions and Deuterium Isotope Effects on the Activities of H+-ATP Synthase from Chloroplasts

We explored the concentration gradient effects of the sodium and lithium ions and the deuterium isotopes effects on the activities of H(+)-ATP synthase from chloroplasts (CF(0)F(1)). We found that the sodium concentration gradient can drive the ATP synthesis reaction of CF(0)F(1). In contrast, the lithium ion can be an efficient enzyme-inhibitor by blocking the entrance channel of the ion translocation pathway in CF(0). In the presence of sodium or lithium ions and with the application of a membrane potential, unexpected enzyme behaviors of CF(0)F(1) were evident. To account for these observations, we propose that both of the sodium and lithium ions could undergo localized hydrolysis reactions in the chemical environment of the ion channel of CF(0). The protons generated locally could proceed to complete the ion translocation process in the ATP synthesis reaction of CF(0)F(1). Experimental and theoretical deuterium isotope effects of the localized hydrolysis on the activities of CF(0)F(1), and the energetics of these related reactions, support this proposed mechanism. Our experimental observations could be understood in the framework of the well-established ion translocation models for the H(+)-ATP synthase from Escherichia coli, and the Na(+)-ATP synthase from Propionigenium modestum and Ilyobacter tartaricus.