TY - JOUR AU1 - Wu, Chia-Fang AU2 - Chen, Hui-Ming AU3 - Sun, Chien-Wen AU4 - Chen, Mei-Lien AU5 - Hsieh, Chia-Jung AU6 - Wang, Shu-Li AU7 - Wu, Ming-Tsang AB - Why was the Taiwan Maternal and Infant Cohort Study (TMICS) established? This cohort was established in response to a food contamination scandal that became news in Taiwan in 2011. In that scandal, endocrine-disrupting phthalates, especially di-(2-ethylhexyl) phthalate (DEHP), were deliberately added to a variety of foods commonly consumed by children there.1 Although the food scandal wound down, environmental exposure to phthalates remains ubiquitous in daily life in Taiwan.2–4 Vulnerable populations such as pregnant women and children can be exposed to these products through different routes, including food ingestion, inhalation and dermal absorption in their daily life.3,5–7 Considering the potential dangers, epidemiologists from northern, central, southern and eastern Taiwan cooperated in establishing this nationwide prospective birth cohort, known as Taiwan Maternal and Infant Cohort Study (TMICS), to study environmental phthalate exposure and the health status of mothers and children in Taiwan. The primary objectives of the TMICS study are: (i) to measure the exposure levels of the common environmental hazardous substances, particularly phthalates, in susceptible populations, including pregnant women and their children; (ii) to examine the effect of maternal exposure to common environmental hazards, particularly phthalates, in Taiwan on a variety of health outcomes in their offspring; (iii) to study the gene-environment interaction; and (iv) to establish a repository of biospecimens for future environmental and health studies. For example, TMICS also plans to analyse the markers of exposure to other potentially hazardous substances in the environment, in order to address a wider range of environment and health concerns. Who is in the cohort? For this multicentre hospital-based birth cohort study, we started in October 2012 to recruit pregnant women who came into nine hospitals (Figure 1a), three in northern Taiwan, three in central Taiwan, two in southern and one in eastern Taiwan, for routine antenatal examinations their third trimester (Weeks 29 to 40). They were enrolled if they were willing to participate in this study. In addition, we also used the enrollees’ previous data if they had been visiting since their first or second trimester (18 weeks and onward). This study was approved by the ethics committees from National Health Research Institutes (NHRI) and the nine hospitals. We excluded those who had histories of systematic diseases such as cancer, hypertension and diabetes or chronic use of corticosteroids or immunosuppressant drugs, those who were more than 45 years old and those who had multiparous pregnancies. As of May 2015, overall 2136 participants participated in this cohort study7 and 1676 women had answered our questionnaires. Of these women, 1638 provided one-spot urine samples during their third trimester for the analysis of 11 phthalate metabolites. After excluding subjects with no urinary creatinine data (N = 7), we were left with the data of 1631 subjects for analyses (Figure 1b). Figure 1 View largeDownload slide Study map (a) and study flow chart (b). Figure 1 View largeDownload slide Study map (a) and study flow chart (b). The mean age [±standard deviation SD)] of 1631 subjects was 31.38 (±4.56) years. About 42.2% of the participant mothers were experiencing their first pregnancy, and most of the participants had college education (81.9%). Less than 6% of them had smoking and drinking habits during pregnancy. The male/female ratio of their newborns was approximately 1: 1. The newborn ages were 38.56 ± 1.27 weeks, with an average height and weight of 49.41 ± 2.25 cm and 3107.71 ± 393.99 g, respectively (Table 1). Table 1. Demographic characteristics of participant mothers and their newborns (n = 1631) Variables Northern Taiwan Middle Taiwan Southern Taiwan East Taiwan Total N 279 617 394 341 1631 Mean ± SD or n (%) Mother  Age (years) 32.55 ± 3.77 31.82 ± 4.28 30.68 ± 4.83 30.88 ± 4.85 31.38 ± 4.56  Education level    US- > EFSA (μg/kg/day) n Mean ± SD Minimum 5th 25th 50th 75th 95th Maximum n (%) DEP 1631 2.61±19.17 0.001 0.005 0.22 0.55 1.58 8.77 560.56 800/500a 0 1 (<0.01) DnBP 1.09 ± 2.06 0.004 0.21 0.43 0.70 1.12 2.79 52.52 100/10 0 14 (0.01) DiBP 0.55 ± 0.71 0.003 0.10 0.23 0.36 0.61 1.52 9.28 −(100/10) 0 0 BBzP 0.06 ± 0.24 0.001 0.002 0.004 0.01 0.06 0.19 7.53 200/500 0 0 DEHP 3.03 ± 4.69 0.043 0.64 1.32 2.03 3.23 7.47 97.22 20/50 21 (1.3) 3 (0.2) Pthalate intake Percentile RfD/TDI (US-/EFSA) > US- > EFSA (μg/kg/day) n Mean ± SD Minimum 5th 25th 50th 75th 95th Maximum n (%) DEP 1631 2.61±19.17 0.001 0.005 0.22 0.55 1.58 8.77 560.56 800/500a 0 1 (<0.01) DnBP 1.09 ± 2.06 0.004 0.21 0.43 0.70 1.12 2.79 52.52 100/10 0 14 (0.01) DiBP 0.55 ± 0.71 0.003 0.10 0.23 0.36 0.61 1.52 9.28 −(100/10) 0 0 BBzP 0.06 ± 0.24 0.001 0.002 0.004 0.01 0.06 0.19 7.53 200/500 0 0 DEHP 3.03 ± 4.69 0.043 0.64 1.32 2.03 3.23 7.47 97.22 20/50 21 (1.3) 3 (0.2) a The TDI value for DEP was from the World Health Organization (WHO, 2003). Table 5. Daily pthalate intake in pregnant women and percent above the threshold of TDI from US-/EFSA in Taiwan (n = 1631) Pthalate intake Percentile RfD/TDI (US-/EFSA) > US- > EFSA (μg/kg/day) n Mean ± SD Minimum 5th 25th 50th 75th 95th Maximum n (%) DEP 1631 2.61±19.17 0.001 0.005 0.22 0.55 1.58 8.77 560.56 800/500a 0 1 (<0.01) DnBP 1.09 ± 2.06 0.004 0.21 0.43 0.70 1.12 2.79 52.52 100/10 0 14 (0.01) DiBP 0.55 ± 0.71 0.003 0.10 0.23 0.36 0.61 1.52 9.28 −(100/10) 0 0 BBzP 0.06 ± 0.24 0.001 0.002 0.004 0.01 0.06 0.19 7.53 200/500 0 0 DEHP 3.03 ± 4.69 0.043 0.64 1.32 2.03 3.23 7.47 97.22 20/50 21 (1.3) 3 (0.2) Pthalate intake Percentile RfD/TDI (US-/EFSA) > US- > EFSA (μg/kg/day) n Mean ± SD Minimum 5th 25th 50th 75th 95th Maximum n (%) DEP 1631 2.61±19.17 0.001 0.005 0.22 0.55 1.58 8.77 560.56 800/500a 0 1 (<0.01) DnBP 1.09 ± 2.06 0.004 0.21 0.43 0.70 1.12 2.79 52.52 100/10 0 14 (0.01) DiBP 0.55 ± 0.71 0.003 0.10 0.23 0.36 0.61 1.52 9.28 −(100/10) 0 0 BBzP 0.06 ± 0.24 0.001 0.002 0.004 0.01 0.06 0.19 7.53 200/500 0 0 DEHP 3.03 ± 4.69 0.043 0.64 1.32 2.03 3.23 7.47 97.22 20/50 21 (1.3) 3 (0.2) a The TDI value for DEP was from the World Health Organization (WHO, 2003). In addition to having measured urinary phthalate metabolites, we also plan to measure other environmental hazards in the stored urine specimens. These include organophosphate pesticides, nonylphenol, bisphenol A, heavy metals, melamine and acrylamide (Table 3). Biochemical data for mothers upon recruitment and for newborns at birth Clinical biochemistry concentrations and those of other important biomarkers collected during the third trimester of the women in this study, as well as those collected from the cord blood of their newborn, were analysed in a central clinical laboratory in Taipei (Tables 2 and 3). That laboratory is officially accredited by Taiwan Accreditation Foundation which uses the same accreditation criteria as those outlined by ISO 15189: 2007. This certification was effective between 16 March 2015 and 15 March 2018 (Certificate No. L1447–150325). The baseline blood analysis for the mothers included the following measurements: (i) thyroid hormones and sex hormones—thyroxine (T4), triiodothyronine (T3), thyroid-stimulating hormone (TSH), free thyroxine (free T4), stradiol (E2), testosterone (TT), progesterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH); (ii) renal function indicators—blood urea nitrogen (BUN), uric acid and creatinine; (iii) biochemical indicators—aspartate aminotransferase (AST), alanine aminotransferase (ALT), sugar AC, insulin, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglyceride; and (iv) routine blood examination—white blood cells (WBC), red blood cells (RBC), platelets, haemoglobin, haematocrit, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), neutrophils, lymphocytes, monocytes, eosinophils and basophils (Table 3). The baseline blood measurements for newborn cord blood included the following: (i) thyroid hormones and sex hormones—thyroxine (T4), triiodothyronine (T3), thyroid-stimulating hormone (TSH), free thyroxine (free T4), estradiol (E2), testosterone (TT), progesterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), free testosterone, albumin, dehydroepiandrosterone sulphate (DHEA-S) and bioavailable testosterone (TESBIO); (ii) growth hormone—insulin-like growth factor-1(IGF1); (ii) immunoglobulin—immunoglobulin E (IgE), multiple allergosorbent chemiluminescent assay (MAST CLA) allergy test; and (iv) routine blood examination—white blood cells (WBC), red blood cells (RBC), platelets, haemoglobin, hamatocrit, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), neutrophils, lymphocytes, monocytes, eosinophils and basophils. What has it found? Key baseline findings Because urinary MiNP, which represents the primary metabolites of DINP (Di-isononyl phthalate), was not detectable in 97.0% (n = 1582/1631), we only present the results of the other 10 urinary phthalate metabolites. The median levels without creatinine correction (ng/ml) for these 10 urinary phthalate metabolites in the third trimester were: 3.35 for MEHP, 8.42 for MEOHP, 10.07 for MEHHP, 14.18 for MECPP, 3.79 for MCMHP, 14.64 for MnBP, 7.56 for MiBP, 0.06 for MBzP, 4.33 for MEP and 5.69 for MMP (Supplementary Table 3, available as Supplementary data at IJE online). After urinary creatinine correction, their median levels (μg/g creatinine) were: 4.91 for MEHP, 12.59 for MEOHP, 14.51 for MEHHP, 20.56 for MECPP, 5.42 for MCMHP, 21.50 for MnBP, 11.28 for MiBP, 0.47 for MBzP, 18.34 for MEP and 8.75 for MMP (Supplementary Table 4, available as Supplementary data at IJE online; Figure 2). In this study, the three metabolites with highest recorded urinary concentrations were MnBP, MECPP and MEP (Supplementary Table 4, available as Supplementary data at IJE online; Figure 2). Figure 2 View largeDownload slide Ten phthalate metabolites of pregnant women in the third trimester from four areas of Taiwan, corrected by creatinine (n = 1631). Figure 2 View largeDownload slide Ten phthalate metabolites of pregnant women in the third trimester from four areas of Taiwan, corrected by creatinine (n = 1631). The concentrations of urinary phthalate metabolites found in this study were lower than those reported by previous studies from Taiwan,3,5,6 suggesting that the phthalate exposures in the general population in Taiwan significantly decreased after the 2011 phthalate food scandal (Table 4). We compared these findings with those of other countries in the same situation, in the third trimester of pregnant women, and found urinary phthalate metabolite concentrations in this study to be generally lower than those reported for European countries,19–23 but generally higher than those reported for Japan.24 Mean and median daily DEHP intake of the participating mothers in the third trimester was 3.03 and 2.03 μg/kg/day, respectively (Table 5). Compared with the recommended tolerable daily intake (TDI) level for DEHP defined by the U.S. Environmental Protection Agency (0.02 mg/kg/day) and the European Food Safety Authority (0.05 mg/kg/day), we found intake of 21 (1.3%) of the women we studied to be above 20 μg/kg/day and in three (0.2%) of them to be above 50 μg/kg/day (Table 5). Based on EFSA TDI, the median HI level, the summation of HQs in the pregnant women was 0.16 (Table 6), a value higher than that reported by a study of pregnant Danish women (0.06) (8–30 gestational weeks)25 and lower than that reported by a study of pregnant Chinese women (0.358).16 Table 6. Hazard quotients (HQ) and hazard indexes (HI) based on TDI (EFSA) and RfD (US EPA) for pregnant women (n = 1631) Phthalate HQ based on EFSA TDI >1 HQ based on US EPA RfD >1 Minimum 25th 50th 95th Maximum n (%) Minimum 25th 50th 95th Maximum n (%) DEP <0.0001 0.0004 0.0011 0.0175 1.1211 1 (0.06) <0.0001 0.0003 0.0007 0.0110 0.7007 0 DnBP 0.0004 0.0430 0.0702 0.2791 5.2524 14 (0.9) <0.0001 0.0043 0.0070 0.0279 0.5252 0 DiBP 0.0003 0.0233 0.0362 0.1521 0.9279 0 <0.0001 0.0023 0.0036 0.0152 0.0928 0 BBzP <0.0001 <0.0001 <0.0001 0.0004 0.0151 0 <0.0001 <0.0001 <0.0001 0.0009 0.0376 0 DEHP 0.0009 0.0265 0.0405 0.1494 1.9443 3 (0.18) 0.0021 0.06621 0.1014 0.3734 4.8608 21 (1.3) HI 0.0036 0.1150 0.1684 0.5517 5.5422 30 (1.8) 0.0029 0.0779 0.1198 0.4116 4.8848 21 (1.3) Phthalate HQ based on EFSA TDI >1 HQ based on US EPA RfD >1 Minimum 25th 50th 95th Maximum n (%) Minimum 25th 50th 95th Maximum n (%) DEP <0.0001 0.0004 0.0011 0.0175 1.1211 1 (0.06) <0.0001 0.0003 0.0007 0.0110 0.7007 0 DnBP 0.0004 0.0430 0.0702 0.2791 5.2524 14 (0.9) <0.0001 0.0043 0.0070 0.0279 0.5252 0 DiBP 0.0003 0.0233 0.0362 0.1521 0.9279 0 <0.0001 0.0023 0.0036 0.0152 0.0928 0 BBzP <0.0001 <0.0001 <0.0001 0.0004 0.0151 0 <0.0001 <0.0001 <0.0001 0.0009 0.0376 0 DEHP 0.0009 0.0265 0.0405 0.1494 1.9443 3 (0.18) 0.0021 0.06621 0.1014 0.3734 4.8608 21 (1.3) HI 0.0036 0.1150 0.1684 0.5517 5.5422 30 (1.8) 0.0029 0.0779 0.1198 0.4116 4.8848 21 (1.3) Table 6. Hazard quotients (HQ) and hazard indexes (HI) based on TDI (EFSA) and RfD (US EPA) for pregnant women (n = 1631) Phthalate HQ based on EFSA TDI >1 HQ based on US EPA RfD >1 Minimum 25th 50th 95th Maximum n (%) Minimum 25th 50th 95th Maximum n (%) DEP <0.0001 0.0004 0.0011 0.0175 1.1211 1 (0.06) <0.0001 0.0003 0.0007 0.0110 0.7007 0 DnBP 0.0004 0.0430 0.0702 0.2791 5.2524 14 (0.9) <0.0001 0.0043 0.0070 0.0279 0.5252 0 DiBP 0.0003 0.0233 0.0362 0.1521 0.9279 0 <0.0001 0.0023 0.0036 0.0152 0.0928 0 BBzP <0.0001 <0.0001 <0.0001 0.0004 0.0151 0 <0.0001 <0.0001 <0.0001 0.0009 0.0376 0 DEHP 0.0009 0.0265 0.0405 0.1494 1.9443 3 (0.18) 0.0021 0.06621 0.1014 0.3734 4.8608 21 (1.3) HI 0.0036 0.1150 0.1684 0.5517 5.5422 30 (1.8) 0.0029 0.0779 0.1198 0.4116 4.8848 21 (1.3) Phthalate HQ based on EFSA TDI >1 HQ based on US EPA RfD >1 Minimum 25th 50th 95th Maximum n (%) Minimum 25th 50th 95th Maximum n (%) DEP <0.0001 0.0004 0.0011 0.0175 1.1211 1 (0.06) <0.0001 0.0003 0.0007 0.0110 0.7007 0 DnBP 0.0004 0.0430 0.0702 0.2791 5.2524 14 (0.9) <0.0001 0.0043 0.0070 0.0279 0.5252 0 DiBP 0.0003 0.0233 0.0362 0.1521 0.9279 0 <0.0001 0.0023 0.0036 0.0152 0.0928 0 BBzP <0.0001 <0.0001 <0.0001 0.0004 0.0151 0 <0.0001 <0.0001 <0.0001 0.0009 0.0376 0 DEHP 0.0009 0.0265 0.0405 0.1494 1.9443 3 (0.18) 0.0021 0.06621 0.1014 0.3734 4.8608 21 (1.3) HI 0.0036 0.1150 0.1684 0.5517 5.5422 30 (1.8) 0.0029 0.0779 0.1198 0.4116 4.8848 21 (1.3) What are the main strengths and weaknesses? This birth cohort, the TMICS cohort, is the first to cover a large sample size of study sites in Taiwan’s four major areas (north, central, south and east). Biomarkers of exposure and outcome were measured in a central laboratory, guaranteeing the high quality of data. One major limitation of this study is that we only measured urinary phthalate metabolites based on a one-spot urine sample taken from the third trimester of pregnant mothers. It is possible that this one measurement cannot represent the entire exposure during the entire duration of pregnancy, particularly if there was a wide variability of urinary phthalate metabolites across three trimesters. Since we have stored urine samples from all three trimesters obtained from the entire birth cohort from the southern Taiwan, we can randomly select some study subjects to measure their urine phthalate metabolites to resolve this question. Can I get hold of the data? Where can I find out more? Collaboration in data analysis and publication will be welcomed and should be sent to the corresponding author at e_encourage@yahoo.com. The dataset of certain demographic characteristics, such as maternal age and education levels and child’s sex, during the study will be available in the Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, at [https://envmed.kmu.edu.tw/index.php/en-GB/data-repository/181-cohort-profile-taiwan-maternal-and-infant-cohort-study-tmics-of-phthalate-exposure-and-health-risk-assessment]. TMICS profile in a nutshell TMICS is a nationwide prospective birth cohort study investigating environmental phthalate exposure and its effects on maternal and child health. Between October 2012 and May 2015, 1631 pregnant women in their third trimester from nine hospitals in Taiwan were recurited, administered questionnaires and asked to provide blood samples and urine samples. Follow-up of pregnant women included short questionnaires (at delivery and 2-3 weeks following delivery) and clinical assessment visits of mother and newborn (at delivery). In October 2016, we started to follow up the study children. The TMICS comprises a wide range of environmental pollutant measures, biochemistry measures and genetic and epigenetic information. TMICS has established a repository of biospecimens of these mothers and children for future environmental and health studies. Certain demographic characteristics of the TMICS dataset are available at [https://envmed.kmu.edu.tw/index.php/en-GB/data-repository/181-cohort-profile-taiwan-maternal-and-infant-cohort-study-tmics-of-phthalate-exposure-and-health-risk-assessment]. Funding The TMICS was supported by Ministry of Education, Republic of China (Taiwan), Ministry of Science and Technology (MOST 106-2314-B-214-007- and MOST 106-2314-B-400-014-MY3), the National Science Council (NSC 100-3114-Y-043-005) and a grant from National Health Research Institutes (grant numbers NHRI EH-102-SP-02; EH-103-SP-02). Neither institution played any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgements We thank all members of the research teams, including following list, who participated in the consortium of this TMICS cohort study. Northern area: Drs Yen-An Tsai, Yu-Fang Huang, Kai-Wei Liao from National Yang Ming University, Taipei, Taiwan; Dr Ming-Song Tsai from Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei, Taiwan; Dr Chih-Yao Chen from Division of Obstetrics and High Risk Pregnancy, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan; Dr Pei-Wei Wang from Department of Pediatrics, Taipei City Hospital, Heping Fuyou Branch, Taipei, Taiwan; Dr Li-Wei Huang from Department of Obstetrics & Gynecology, Taipei City Hospital, Heping Fuyou Branch, Taipei, Taiwan. Middle area: Ms Hui-Chun Chen and the obstetricians and paediatricians for subject recruitments, data collections and specimen collections: Dr Ying-Chih Tseng from the Department of Obstetrics and Gynecology, Hsinchu Cathay General Hospital, Hsinchu, Taiwan; Dr Chaw-Liang Chang from the Department of Pediatrics, Hsinchu Cathay General Hospital, Hsinchu, Taiwan; Dr Tsung-Ho Ying from the Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan; Dr Pen-Hua Su from Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan; Dr Kuei-Cheng Hsu from the Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua, Taiwan; Dr Hsiao-Neng Chen and Dr Jian-Wun Cian. from Department of Pediatrics, Changhua Christian Hospital, Changhua, Taiwan. Southern area: Ms Shiang-Shiun Chen, Yun-Shan Tsai, Sheng-Wen Su, Ching-Yi Chen and the obstetricians and paediatricians for subject recruitments, data collections and specimen collections: Dr Fu-Chen Kuo from Department of Gynecology and Obstetrics, E-Da Hospital, Kaohsiung, Taiwan; Dr Chien-Yi Wu from Department of Pediatrics, E-Da Hospital, Kaohsiung, Taiwan; Dr Yung-Hung Chen from Department of Obstetrics and Gynecology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan; Dr Chiu-Lin Wang from Department of Obstetrics and Gynecology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan; Dr Cheng-Yu Long from Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Dr Chih-Hsing Hung from Department of Pediatrics, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan; Dr Wei-Der Lee from Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Ms Chun-Chi Huang from Department of Medicine Laboratory, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan. East area: Dr Yu‐Hsun Chang from Department of Pediatrics, Buddhist Tzu Chi General Hospital, Hualien, Taiwan; Dr Sheng-Po Kao and Dr Yu-Chi Wei from Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan; Dr Anren Hu from Department of Laboratory Medicine and Biotechnology, Tzu Chi University, Hualien, Taiwan. Conflict of interest: None declared. References 1 Wu MT , Wu CF , Wu JR et al. The public health threat of phthalate-tainted foodstuffs in Taiwan: the policies the government implemented and the lessons we learned . Environment Int 2012 ; 44 : 75 – 9 . Google Scholar Crossref Search ADS 2 Wu CF , Chen BH , Shiea J et al. Temporal changes of urinary oxidative metabolites of di(2-ethylhexyl)phthalate after the 2011 phthalate incident in Taiwanese children: findings of a six month follow-up . Environ Sci Technol 2013 ; 47 : 13754 – 62 . Google Scholar Crossref Search ADS PubMed 3 Kuo FC , Su SW , Wu CF et al. Relationship of urinary phthalate metabolites with serum thyroid hormones in pregnant women and their newborns: a prospective birth cohort in Taiwan . PLoS One 2015 ; 10 : e0123884. Google Scholar Crossref Search ADS PubMed 4 Chang JW , Lee CC , Pan WH et al. Estimated daily intake and cumulative risk assessment of phthalates in the General Taiwanese after the 2011 DEHP Food Scandal . Sci Rep 2017 ; 7 : 45009. Google Scholar Crossref Search ADS PubMed 5 Lin S , Ku HY , Su PH et al. Phthalate exposure in pregnant women and their children in central Taiwan . Chemosphere 2011 ; 82 : 947 – 55 . Google Scholar Crossref Search ADS PubMed 6 Lin LC , Wang SL , Chang YC et al. Associations between maternal phthalate exposure and cord sex hormones in human infants . Chemosphere 2011 ; 83 : 10 – 23 . 7 Tsai YA , Tsai MS , Hou JW et al. 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 . Sci Total Environ 2018 ; 618: 635 – 44 . Google Scholar Crossref Search ADS PubMed 8 Su PH , Chang CK , Lin CY et al. Prenatal exposure to phthalate ester and pubertal development in a birth cohort in central Taiwan: a 12-year follow-up study . Environ Res 2015 ; 136 : 324 – 30 . Google Scholar Crossref Search ADS PubMed 9 Dewalque L , Charlier C , Pirard C. Estimated daily intake and cumulative risk assessment of phthalate diesters in a Belgian general population . Toxicol Lett 2014 ; 231 : 161 – 68 . Google Scholar Crossref Search ADS PubMed 10 Harper HA , Rodwell VW , Mayes PA. Review of Physiological Chemistry , 16 th edn. New York, NY : McGraw-Hil , 1977 . 11 Chen ML , Chen JS , Tang CL , Mao IF. The internal exposure of Taiwanese to phthalate - evidence of intensive use of plastic materials . Environ Int 2008 ; 34 : 79 – 85 . Google Scholar Crossref Search ADS PubMed 12 Koch HM , Preuss R , Angerer J. Di(2-ethylhexyl)phthalate (DEHP): human metabolism and internal exposure - an update and latest results . Int J Androl 2006 ; 29 : 155 – 65 . Google Scholar Crossref Search ADS PubMed 13 Anderson WA , Castle L , Scotter MJ , Massey RC , Springall C. A biomarker approach to measuring human dietary exposure to certain phthalate diesters . Food Addit Contam 2001 ; 18 : 1068 – 74 . Google Scholar Crossref Search ADS PubMed 14 Koch HM , Christensen KL , Harth V , Lorber M , Bruning T. Di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP) metabolism in a human volunteer after single oral doses . Arch Toxicol 2012 ; 86 : 1829 – 39 . Google Scholar Crossref Search ADS PubMed 15 Koch HM , Wittassek M , Bruning T , Angerer J , Heudorf U. Exposure to phthalates in 5-6 years old primary school starters in Germany - A human biomonitoring study and a cumulative risk assessment . Int J Hyg Environ Health 2011 ; 214 : 188 – 95 . Google Scholar Crossref Search ADS PubMed 16 Gao H , Xu YY , Huang K et al. Cumulative risk assessment of phthalates associated with birth outcomes in pregnant Chinese women: a prospective cohort study . Environ Pollut 2017 ; 222 : 549 – 56 . Google Scholar Crossref Search ADS PubMed 17 Borch J , Axelstad M , Vinggaard AM , Dalgaard M. Diisobutyl phthalate has comparable anti-androgenic effects to di-n-butyl phthalate in fetal rat testis . Toxicol Lett 2006 ; 163 : 183 – 90 . Google Scholar Crossref Search ADS PubMed 18 WHO (World Health Organization) . Diethyl Phthalate. Concise International Chemical Assessment Document 52. 2003 . http://www.who.int/ipcs/publications/cicad/en/cicad52.pdf (20 April 2018, date last accessed). 19 Ye X , Pierik FH , Hauser R et al. Urinary metabolite concentrations of organophosphorous pesticides, bisphenol A, and phthalates among pregnant women in Rotterdam, the Netherlands: the Generation R study . Environ Res 2008 ; 108 : 260 – 67 . Google Scholar Crossref Search ADS PubMed 20 Berman T , Hochner-Celnikier D , Calafat AM et al. Phthalate exposure among pregnant women in Jerusalem, Israel: results of a pilot study . Environ Int 2009 ; 35 : 353 – 57 . Google Scholar Crossref Search ADS PubMed 21 Zeman FA , Boudet C , Tack K et al. Exposure assessment of phthalates in French pregnant women: results of the ELFE pilot study . Int J Hyg Environ Health 2013 ; 216 : 271 – 79 . Google Scholar Crossref Search ADS PubMed 22 Polanska K , Ligocka D , Sobala W , Hanke W. Phthalate exposure and child development: the Polish Mother and Child Cohort Study . Early Hum Dev 2014 ; 90 : 477 – 85 . Google Scholar Crossref Search ADS PubMed 23 Valvi D , Monfort N , Ventura R et al. Variability and predictor of urinary phthalate metabolites in Spanish pregnant women . Int J Hyg Environ Health 2015 ; 218 : 220 – 31 . Google Scholar Crossref Search ADS PubMed 24 Suzuki Y , Niwa M , Yoshinaga J et al. Exposure assessment of phthalate esters in Japanese pregnant women by using urinary metabolites analysis . Environ Health Prev Med 2009 ; 14 : 180 – 87 . Google Scholar Crossref Search ADS PubMed 25 Tefre de Renzy-Martin K , Frederiksen H , Christensen JS et al. Current exposure of 200 pregnant Danish women to phthalates, parabens and phenols . Reproduction 2014 ; 147 : 443 – 53 . Google Scholar Crossref Search ADS PubMed © The Author(s) 2018; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) TI - Cohort Profile: The Taiwan Maternal and Infant Cohort Study (TMICS) of phthalate exposure and health risk assessment JF - International Journal of Epidemiology DO - 10.1093/ije/dyy067 DA - 2018-08-01 UR - https://www.deepdyve.com/lp/oxford-university-press/cohort-profile-the-taiwan-maternal-and-infant-cohort-study-tmics-of-dLj9Se7Dc0 SP - 1047 EP - 1047j VL - 47 IS - 4 DP - DeepDyve ER -