Top

Environmental Health and Preventive Medicine

Published in:

Open Access 01-12-2017 | Research article

The Hokkaido Birth Cohort Study on Environment and Children’s Health: cohort profile—updated 2017

Authors: Reiko Kishi, Atsuko Araki, Machiko Minatoya, Tomoyuki Hanaoka, Chihiro Miyashita, Sachiko Itoh, Sumitaka Kobayashi, Yu Ait Bamai, Keiko Yamazaki, Ryu Miura, Naomi Tamura, Kumiko Ito, Houman Goudarzi, the members of The Hokkaido Study on Environment and Children’s Health

Published in: Environmental Health and Preventive Medicine | Issue 1/2017

Abstract

The Hokkaido Study on Environment and Children’s Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary study goals are (1) to examine the effects of low-level environmental chemical exposures on birth outcomes, including birth defects and growth retardation; (2) to follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders and perform a longitudinal observation of child development; (3) to identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) to identify the additive effects of various chemicals, including tobacco smoking. The purpose of this report is to update the progress of the Hokkaido Study, to summarize the recent results, and to suggest future directions. In particular, this report provides the basic characteristics of the cohort populations, discusses the population remaining in the cohorts and those who were lost to follow-up at birth, and introduces the newly added follow-up studies and case-cohort study design. In the Sapporo cohort of 514 enrolled pregnant women, various specimens, including maternal and cord blood, maternal hair, and breast milk, were collected for the assessment of exposures to dioxins, polychlorinated biphenyls, organochlorine pesticides, perfluoroalkyl substances, phthalates, bisphenol A, and methylmercury. As follow-ups, face-to-face neurobehavioral developmental tests were conducted at several different ages. In the Hokkaido cohort of 20,926 enrolled pregnant women, the prevalence of complicated pregnancies and birth outcomes, such as miscarriage, stillbirth, low birth weight, preterm birth, and small for gestational age were examined. The levels of exposure to environmental chemicals were relatively low in these study populations compared to those reported previously. We also studied environmental chemical exposure in association with health outcomes, including birth size, neonatal hormone levels, neurobehavioral development, asthma, allergies, and infectious diseases. In addition, genetic and epigenetic analyses were conducted. The results of this study demonstrate the effects of environmental chemical exposures on genetically susceptible populations and on DNA methylation. Further study and continuous follow-up are necessary to elucidate the combined effects of chemical exposure on health outcomes.

Colborn T, Dumanoski D, Myers J. Our stolen future: are we threatening our fertility, intelligence, and survival? A scientific detective story. New York: Plume; 1997.

Meeker JD. Exposure to environmental endocrine disruptors and child development. Arch Pediatr Adolesc Med. 2012;166:E1–7.CrossRefPubMedPubMedCentral

Schug TT, Janesick A, Blumberg B, Heindel JJ. Endocrine disrupting chemicals and disease susceptibility. J Steroid Biochem Mol Biol. 2011;127:204–15.CrossRefPubMedPubMedCentral

Wigle DT, Arbuckle TE, Turner MC, Berube A, Yang Q, Liu S, et al. Epidemiologic evidence of relationships between reproductive and child health outcomes and environmental chemical contaminants. J Toxicol Environ Health B Crit Rev. 2008;11:373–517.CrossRefPubMed

Okada E, Kashino I, Matsuura H, Sasaki S, Miyashita C, Yamamoto J, et al. Temporal trends of perfluoroalkyl acids in plasma samples of pregnant women in Hokkaido, Japan, 2003-2011. Environ Int. 2013;60:89–96.CrossRefPubMed

Kishi R, Zhang J, Ha E, Chen P, Tian Y, Xia Y, et al. Birth Cohort Consortium of Asia (BiCCA)—current and future perspectives. Epidemiology. 2016. In press.

Kishi R, Kobayashi S, Ikeno T, Araki A, Miyashita C, Itoh S, et al. Ten years of progress in the Hokkaido Birth Cohort Study on Environment and Children’s Health: cohort profile—updated 2013. Environ Health Prev Med. 2013;18:429–50.CrossRefPubMedPubMedCentral

Boyle CA, Boulet S, Schieve LA, Cohen RA, Blumberg SJ, Yeargin-Allsopp M, et al. Trends in the prevalence of developmental disabilities in us children, 1997-2008. Pediatrics. 2011;127:1034–42.CrossRefPubMed

Pastor PN, Reuben CA, Duran CR. Identifying emotional and behavioral problems in children aged 4-17 years: United States, 2001-2007. Natl Health Stat Report. 2012;1-17

10.

Jackson KD, Howie LD, Akinbami LJ. Trends in allergic conditions among children: United States, 1997-2011. NCHS Data Brief. 2013;1-8

11.

Brozek G, Lawson J, Szumilas D, Zejda J. Increasing prevalence of asthma, respiratory symptoms, and allergic diseases: four repeated surveys from 1993-2014. Respir Med. 2015;109:982–90.CrossRefPubMed

12.

Leenen FA, Muller CP, Turner JD. DNA methylation: conducting the orchestra from exposure to phenotype? Clin Epigenetics. 2016;8:92.CrossRefPubMedPubMedCentral

13.

Kishi R, Sasaki S, Yoshioka E, Yuasa M, Sata F, Saijo Y, et al. Cohort profile: the Hokkaido Study on Environment and Children’s Health in Japan. Int J Epidemiol. 2011;40:611–8.CrossRefPubMed

14.

Survey of obstetrics medical institution, 2008. General Affairs Division, Health Policy Bureau, Ministry of Health, Labour and Welfare. http://www.mhlw.go.jp/topics/bukyoku/isei/kinkyu/dl/01d.pdf (in Japanese). Accessed 21 Mar 2017.

15.

Mitsui T, Araki A, Imai A, Sato S, Miyashita C, Ito S, et al. Effects of prenatal Leydig cell function on the ratio of the second to fourth digit lengths in school-aged children. PLoS One. 2015;10, e0120636.CrossRefPubMedPubMedCentral

16.

Todaka T, Hirakawa H, Kajiwara J, Hori T, Tobiishi K, Onozuka D, et al. Concentrations of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and dioxin-like polychlorinated biphenyls in blood collected from 195 pregnant women in Sapporo city, Japan. Chemosphere. 2007;69:1228–37.CrossRefPubMed

17.

Todaka T, Hirakawa H, Kajiwara J, Hori T, Tobiishi K, Onozuka D, et al. Concentrations of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and dioxin-like polychlorinated biphenyls in blood and breast milk collected from 60 mothers in Sapporo city, Japan. Chemosphere. 2008;72:1152–8.CrossRefPubMed

18.

Todaka T, Hori T, Hirakawa H, Kajiwara J, Yasutake D, Onozuka D, et al. Congener-specific analysis of non-dioxin-like polychlorinated biphenyls in blood collected from 195 pregnant women in Sapporo city, Japan. Chemosphere. 2008;73:923–31.CrossRefPubMed

19.

Inoue K, Okada F, Ito R, Kato S, Sasaki S, Nakajima S, et al. Perfluorooctane sulfonate (PFOS) and related perfluorinated compounds in human maternal and cord blood samples: assessment of PFOS exposure in a susceptible population during pregnancy. Environ Health Perspect. 2004;112:1204–7.CrossRefPubMedPubMedCentral

20.

Miyashita C, Sasaki S, Saijo Y, Okada E, Kobayashi S, Baba T, et al. Demographic, behavioral, dietary, and socioeconomic characteristics related to persistent organic pollutants and mercury levels in pregnant women in Japan. Chemosphere. 2015;133:13–21.CrossRefPubMed

21.

Sasaki S, Braimoh TS, Yila TA, Yoshioka E, Kishi R. Self-reported tobacco smoke exposure and plasma cotinine levels during pregnancy—a validation study in northern Japan. Sci Total Environ. 2011;412:114–8.CrossRefPubMed

22.

Sasaki S, Kondo T, Sata F, Saijo Y, Katoh S, Nakajima S, et al. Maternal smoking during pregnancy and genetic polymorphisms in the Ah receptor, CYP1A1 and GSTM1 affect infant birth size in Japanese subjects. Mol Hum Reprod. 2006;12:77–83.CrossRefPubMed

23.

Spurgeon SL, Jones RC, Ramakrishnan R. High throughput gene expression measurement with real-time PCR in a microfluidic dynamic array. PLoS One. 2008;3, e1662.CrossRefPubMedPubMedCentral

24.

Wang B, Tan HW, Fang W, Meinhardt LW, Mischke S, Matsumoto T, et al. Developing single nucleotide polymorphism (SNP) markers from transcriptome sequences for identification of longan (Dimocarpus longan) germplasm. Hortic Res. 2015;2:14065.CrossRefPubMedPubMedCentral

25.

Wang J, Lin M, Crenshaw A, Hutchinson A, Hicks B, Yeager M, et al. High-throughput single nucleotide polymorphism genotyping using nanofluidic dynamic arrays. BMC Genomics. 2009;10:561.CrossRefPubMedPubMedCentral

26.

Kobayashi S, Azumi K, Goudarzi H, Araki A, Miyashita C, Kobayashi S, et al. Effects of prenatal perfluoroalkyl acid exposure on cord blood IGF2/H19 methylation and ponderal index: The Hokkaido Study. J Expo Sci Environ Epidemiol. 2017;27:251–9.CrossRefPubMed

27.

Bibikova M, Barnes B, Tsan C, Ho V, Klotzle B, Le JM, et al. High density DNA methylation array with single CpG site resolution. Genomics. 2011;98:288–95.CrossRefPubMed

28.

Sandoval J, Heyn H, Moran S, Serra-Musach J, Pujana MA, Bibikova M, et al. Validation of a DNA methylation microarray for 450,000 CpG sites in the human genome. Epigenetics. 2011;6:692–702.CrossRefPubMed

29.

Itabashi K, Miura F, Uehara R, Nakamura Y. New Japanese neonatal anthropometric charts for gestational age at birth. Pediatr Int. 2014;56(5):702–8.CrossRefPubMed

30.

Hanaoka T, Tamura N, Ito K, Sasaki S, Araki A, Ikeno T, et al. Prevalence and risk of birth defects observed in a prospective cohort study; the Hokkaido Study on Environment and Children’s Health. J Epidemiol. 2017. In press.

31.

Kanazawa A, Miyasita C, Okada E, Kobayashi S, Washino N, Sasaki S, et al. Blood persistent organochlorine pesticides in pregnant women in relation to physical and environmental variables in the Hokkaido Study on Environment and Children’s Health. Sci Total Environ. 2012;426:73–82.CrossRefPubMed

32.

Okada E, Sasaki S, Kashino I, Matsuura H, Miyashita C, Kobayashi S, et al. Prenatal exposure to perfluoroalkyl acids and allergic diseases in early childhood. Environ Int. 2014;65:127–34.CrossRefPubMed

33.

Konishi K, Sasaki S, Kato S, Ban S, Washino N, Kajiwara J, et al. Prenatal exposure to PCDDs/PCDFs and dioxin-like PCBs in relation to birth weight. Environ Res. 2009;109:906–13.CrossRefPubMed

34.

Washino N, Saijo Y, Sasaki S, Kato S, Ban S, Konishi K, et al. Correlations between prenatal exposure to perfluorinated chemicals and reduced fetal growth. Environ Health Perspect. 2009;117:660–7.CrossRefPubMed

35.

Minatoya M, Araki A, Miyashita C, Sasaki S, Goto Y, Nakajima T, et al. Prenatal di-2-ethylhexyl phthalate exposure and cord blood adipokine levels and birth size: The Hokkaido Study on Environment and Children’s Health. Sci Total Environ. 2017;579:606–11.CrossRefPubMed

36.

Miyashita C, Sasaki S, Ikeno T, Araki A, Ito S, Kajiwara J, et al. Effects of in utero exposure to polychlorinated biphenyls, methylmercury, and polyunsaturated fatty acids on birth size. Sci Total Environ. 2015;533:256–65.CrossRefPubMed

37.

Minatoya M, Itoh S, Miyashita C, Araki A, Sasaki S, Iwasaki Y, et al. Association of prenatal exposure to perfluoroalkyl substances with cord blood adipokines: The Hokkaido Study on Environment and Children’s Health. Environ Res. 2017;156:175–82.CrossRefPubMed

38.

Kato S, Itoh S, Yuasa M, Baba T, Miyashita C, Sasaki S, et al. Association of perfluorinated chemical exposure in utero with maternal and infant thyroid hormone levels in the Sapporo cohort of Hokkaido Study on the Environment and Children’s Health. Environ Health Prev Med. 2016;21(5):334–44.CrossRefPubMed

39.

Minatoya M, Nakajima S, Sasaki S, Araki A, Miyashita C, Ikeno T, et al. Effects of prenatal phthalate exposure on thyroid hormone levels, mental and psychomotor development of infants: The Hokkaido Study on Environment and Children’s Health. Sci Total Environ. 2016;565:1037–43.CrossRefPubMed

40.

Minatoya M, Sasaki S, Araki A, Miyashita C, Itoh S, Yamamoto J, et al. Cord blood bisphenol A levels and reproductive and thyroid hormone levels of neonates: The Hokkaido Study on Environment and Children’s Health. Epidemiology. 2017; Special Issue. In press.

41.

Baba T, Yoshioka E, Sasaki S, Miyashita C, Yuasa M, Itoh S, Kajiwara J, Todaka T, Kato S, Kobatasi S, Okada E, Kashino I, Yila T.A, Braimoh T, Kishi R. Levels of PCB congeners in maternal blood and their effect on maternal and neonatal thyroid hormones—result from Hokkaido Study on Environment and Children’s Health. The 6th International Congress of Asian Society of Toxicology (ASIATOX-VI). Sendai, Miyagi, Japan. 2012.

42.

Araki A, Mitsui T, Miyashita C, Nakajima T, Naito H, Ito S, et al. Association between maternal exposure to di(2-ethylhexyl) phthalate and reproductive hormone levels in fetal blood: The Hokkaido Study on Environment and Children’s Health. PLoS One. 2014;9, e109039.CrossRefPubMedPubMedCentral

43.

Araki A, Mitsui T, Goudarzi H, Nakajima T, Miyashita C, Itoh S, et al. Prenatal di(2-ethylhexyl) phthalate exposure and disruption of adrenal androgens and glucocorticoids levels in cord blood: The Hokkaido Study. Sci Total Environ. 2017;581-582:297–304.CrossRefPubMed

44.

Goudarzi H, Araki A, Itoh S, Sasaki S, Miyashita C, Mitsui T, et al. The association of prenatal exposure to perfluorinated chemicals with glucocorticoid and androgenic hormones in cord blood samples: The Hokkaido Study. Environ Health Perspect. 2017;125:111–8.PubMed

45.

Itoh S, Araki A, Mitsui T, Miyashita C, Goudarzi H, Sasaki S, et al. Association of perfluoroalkyl substances exposure in utero with reproductive hormone levels in cord blood in the Hokkaido Study on Environment and Children’s Health. Environ Int. 2016;94:51–9.CrossRefPubMed

46.

Nakajima S, Saijo Y, Kato S, Sasaki S, Uno A, Kanagami N, et al. Effects of prenatal exposure to polychlorinated biphenyls and dioxins on mental and motor development in Japanese children at 6 months of age. Environ Health Perspect. 2006;114:773–8.CrossRefPubMed

47.

Goudarzi H, Nakajima S, Ikeno T, Sasaki S, Kobayashi S, Miyashita C, et al. Prenatal exposure to perfluorinated chemicals and neurodevelopment in early infancy: The Hokkaido Study. Sci Total Environ. 2016;541:1002–10.CrossRefPubMed

48.

Minatoya M, Sasaki S, Nakajima S, Yamamoto J, Araki A, Itoh S, et al. Prenatal bisphenol A exposure and birth outcomes: The Hokkaido Study. In 2014 Conference of International Society for Environmental Epidemiology Asia Chapter. Shanghai, China; 2014.

49.

Nakajima S, Sasaki S, Kato S, Nakamura Y, Sengoku Y, Kajiwara J, et al. Effects of prenatal exposure to polychlorinated biphenyls and dioxins on mental and motor development in Japanese children at 6 and 18 month. In Annual Conference of the Japanese Society for Hygiene Kanazwa, Japan; 24-26 March, 2014.

50.

Minatoya M, Itoh S, Araki A, Tamura N, Yamazaki K, Nishihara S, et al. Associated factors of behavioural problems in children at preschool age: The Hokkaido Study on Environment and Children’s Health. Child Care Health Dev. 2016.

51.

Kita T, Nakajima S, Ikeno T, Kishi R. The association between parental socioeconomic status and intellectual ability in Japanese infants aged 42 month: The Hokkaido Study. In International Epidemiological Association 2014, World Congress of Epidemiology; Anchorage, Alaska, USA. 17-24 August 2014

52.

Third council for promotion of measures against allergies [http://www.mhlw.go.jp/stf/shingi2/0000121262.html]. Accessed 21 Mar 2017.

53.

Miyashita C, Sasaki S, Saijo Y, Washino N, Okada E, Kobayashi S, et al. Effects of prenatal exposure to dioxin-like compounds on allergies and infections during infancy. Environmen Res. 2011;111:551–8.CrossRef

54.

Okada E, Sasaki S, Saijo Y, Washino N, Miyashita C, Kobayashi S, et al. Prenatal exposure to perfluorinated chemicals and relationship with allergies and infectious diseases in infants. Environ Res. 2012;112:118–25.CrossRefPubMed

55.

Goudarzi H, Miyashita C, Okada E, Kashino I, Chen C-J, Ito S, et al. Prenatal exposure to perfluoroalkyl acids and prevalence of infectious diseases up to 4 years of age. Environ Int. 2017, in press.

56.

Goudarzi H, Miyashita C, Okada E, Kashino I, Kobayashi S, Chen CJ, et al. Effects of prenatal exposure to perfluoroalkyl acids on prevalence of allergic diseases among 4-year-old children. Environ Int. 2016;94:124–32.CrossRefPubMed

57.

Kishi R, Nakajima T, Goudarzi H, Kobayashi S, Sasaki S, Okada E, et al. The association of prenatal exposure to perfluorinated chemicals with maternal essential and long-chain polyunsaturated fatty acids during pregnancy and the birth weight of their offspring: The Hokkaido Study. Environ Health Perspect. 2015;123:1038–45.CrossRefPubMedPubMedCentral

58.

Jia X, Harada Y, Tagawa M, Naito H, Hayashi Y, Yetti H, et al. Prenatal maternal blood triglyceride and fatty acid levels in relation to exposure to di(2-ethylhexyl)phthalate: a cross-sectional study. Environ Health Preven Med. 2015;20:168–78.CrossRef

59.

Kobayashi S, Sata F, Miyashita C, Sasaki S, Ban S, Araki A, et al. Dioxin-metabolizing genes in relation to effects of prenatal dioxin levels and reduced birth size: The Hokkaido Study. Reprod Toxicol. 2016;67:111–6.CrossRefPubMed

60.

Kobayashi S, Sata F, Sasaki S, Ban S, Miyashita C, Okada E, et al. Genetic association of aromatic hydrocarbon receptor (AhR) and cytochrome p450, family 1, subfamily a, polypeptide 1 (CYP1A1) polymorphisms with dioxin blood concentrations among pregnant Japanese women. Toxicol Lett. 2013;219:269–78.CrossRefPubMed

61.

Kobayashi S, Sata F, Sasaki S, Braimoh TS, Araki A, Miyashita C, et al. Combined effects of AhR, CYP1A1, and XRCC1 genotypes and prenatal maternal smoking on infant birth size: biomarker assessment in the Hokkaido Study. Reprod Toxicol. 2016;65:295–306.CrossRefPubMed

62.

Sasaki S, Sata F, Katoh S, Saijo Y, Nakajima S, Washino N, et al. Adverse birth outcomes associated with maternal smoking and polymorphisms in the n-nitrosamine-metabolizing enzyme genes NQO1 and CYP2E1. Am J Epidemiol. 2008;167:719–26.CrossRefPubMed

63.

Yila TA, Sasaki S, Miyashita C, Braimoh TS, Kashino I, Kobayashi S, et al. Effects of maternal 5,10-methylenetetrahydrofolate reductase c677t and a1298c polymorphisms and tobacco smoking on infant birth weight in a Japanese population. J Epidemiol. 2012;22:91–102.CrossRefPubMedPubMedCentral

64.

Hayes AF. Introduction to mediation, moderation, and conditional process analysis: a regression-based approach. New York, NY, USA: Guilford Press; 2013.

65.

Ashley-Martin J, Dodds L, Arbuckle TE, Bouchard MF, Fisher M, Morriset AS, et al. Maternal concentrations of perfluoroalkyl substances and fetal markers of metabolic function and birth weight. Am J Epidemiol. 2017;185:185–93.PubMedPubMedCentral

66.

Fei C, Olsen J. Prenatal exposure to perfluorinated chemicals and behavioral or coordination problems at age 7 years. Environ Health Perspect. 2011;119:573–8.CrossRefPubMed

67.

Lee YJ, Kim MK, Bae J, Yang JH. Concentrations of perfluoroalkyl compounds in maternal and umbilical cord sera and birth outcomes in Korea. Chemosphere. 2013;90:1603–9.CrossRefPubMed

68.

Maisonet M, Terrell ML, McGeehin MA, Christensen KY, Holmes A, Calafat AM, et al. Maternal concentrations of polyfluoroalkyl compounds during pregnancy and fetal and postnatal growth in British girls. Environ Health Perspect. 2012;120:1432–7.CrossRefPubMedPubMedCentral

69.

Starling AP, Engel SM, Whitworth KW, Richardson DB, Stuebe AM, Daniels JL, et al. Perfluoroalkyl substances and lipid concentrations in plasma during pregnancy among women in the Norwegian Mother and Child Cohort Study. Environ Int. 2014;62:104–12.CrossRefPubMed

70.

Stein CR, Wolff MS, Calafat AM, Kato K, Engel SM. Comparison of polyfluoroalkyl compound concentrations in maternal serum and amniotic fluid: a pilot study. Reprod Toxicol. 2012;34:312–6.CrossRefPubMedPubMedCentral

71.

Ait Bamai Y, Araki A, Kawai T, Tsuboi T, Saito I, Yoshioka E, et al. Associations of phthalate concentrations in floor dust and multi-surface dust with the interior materials in Japanese dwellings. Sci Total Environ. 2014;468-469:147–57.CrossRefPubMed

72.

Ait Bamai Y, Araki A, Kawai T, Tsuboi T, Yoshioka E, Kanazawa A, et al. Comparisons of urinary phthalate metabolites and daily phthalate intakes among Japanese families. Int J Hyg Environ Health. 2015;218:461–70.CrossRefPubMed

73.

Yamamoto J, Minatoya M, Sasaki S, Araki A, Miyashita C, Matsumura T, et al. Quantifying bisphenol A in maternal and cord whole blood using isotope dilution liquid chromatography/tandem mass spectrometry and maternal characteristics associated with bisphenol A. Chemosphere. 2016;164:25–31.CrossRefPubMed

74.

Gynecology JSoOa: Definition of miscarriage and preterm birth (in Japanese). Acta Obstet Gynaecol Jap. 1992;44

75.

Statistics and Information Department Ministry of Health Labour and Welfare. Vital statistics of Japan, 2012. Tokyo: Health Labour and Welfare Statistics Association; 2012.

76.

Zhang J, Savitz DA. Duration of gestation and timing of birth. In: Buck Louis GM, Platt RW, editors. Reproductive and perinatal epidemiology. NY: Oxford University Press; 2011. p. 152–67.CrossRef

77.

Hack M, Taylor HG, Klein N, Eiben R, Schatschneider C, Mercuri-Minich N. School-age outcomes in children with birth weights under 750 g. N Engl J Med. 1994;331:753–9.CrossRefPubMed

78.

Tanabe K, Tamakoshi K, Kikuchi S, Murotsuki J. Learning disability in 10- to 16-year-old adolescents with very low birth weight in Japan. Tohoku J Exp Med. 2014;232:27–33.CrossRefPubMed

79.

Kjeldsen LS, Bonefeld-Jorgensen EC. Perfluorinated compounds affect the function of sex hormone receptors. Environ Sci Pollut Res Int. 2013;20:8031–44.CrossRefPubMed

80.

Lovekamp-Swan T, Jetten AM, Davis BJ. Dual activation of PPARalpha and PPARgamma by mono-(2-ethylhexyl) phthalate in rat ovarian granulosa cells. Mol Cell Endocrinol. 2003;201:133–41.CrossRefPubMed

81.

Vanden Heuvel JP, Thompson JT, Frame SR, Gillies PJ. Differential activation of nuclear receptors by perfluorinated fatty acid analogs and natural fatty acids: a comparison of human, mouse, and rat peroxisome proliferator-activated receptor-α, -β, and -γ, liver x receptor-β, and retinoid x receptor-α. Toxicol Sci. 2006;92:476–89.CrossRefPubMed

82.

Smialowicz RJ, DeVito MJ, Williams WC, Birnbaum LS. Relative potency based on hepatic enzyme induction predicts immunosuppressive effects of a mixture of PCDDs/PCDFs and PCBs. Toxicol Appl Pharmacol. 2008;227:477–84.CrossRefPubMed

83.

Grandjean PEW, Andersen E, Budtz-Jorgensen F, Nielsen K, Molbak P, Weihe C, et al. Serum vaccine antibody concentrations in children exposed to perfluorinated compounds. JAMA. 2012;307:391–7.CrossRefPubMedPubMedCentral

84.

Keil DE, Mehlmann T, Butterworth L, Peden-Adams MM. Gestational exposure to perfluorooctane sulfonate suppresses immune function in B6C3F1 mice. Toxicol Sci. 2008;103:77–85.CrossRefPubMed

85.

Joubert BR, Felix JF, Yousefi P, Bakulski KM, Just AC, Breton C, et al. DNA methylation in newborns and maternal smoking in pregnancy: genome-wide consortium meta-analysis. Am J Hum Genet. 2016;98:680–96.CrossRefPubMedPubMedCentral

86.

Gruzieva O, Xu CJ, Breton CV, Annesi-Maesano I, Anto JM, Auffray C, et al. Epigenome-wide meta-analysis of methylation in children related to prenatal NO2 air pollution exposure. Environ Health Perspect. 2017;125:104–10.PubMed

Title: The Hokkaido Birth Cohort Study on Environment and Children’s Health: cohort profile—updated 2017
Authors: Reiko Kishi
Atsuko Araki
Machiko Minatoya
Tomoyuki Hanaoka
Chihiro Miyashita
Sachiko Itoh
Sumitaka Kobayashi
Yu Ait Bamai
Keiko Yamazaki
Ryu Miura
Naomi Tamura
Kumiko Ito
Houman Goudarzi
the members of The Hokkaido Study on Environment and Children’s Health
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Environmental Health and Preventive Medicine / Issue 1/2017
Print ISSN: 1342-078X
Electronic ISSN: 1347-4715
DOI: https://doi.org/10.1186/s12199-017-0654-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The Hokkaido Birth Cohort Study on Environment and Children’s Health: cohort profile—updated 2017

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2017

Effects of gaps in priorities between ideal and real lives on psychological burnout among academic faculty members at a medical university in Japan: a cross-sectional study

Characteristics of stepfamilies and maternal mental health compared with non-stepfamilies in Japan

The impact of different lenses on visual and musculoskeletal complaints in VDU workers with work-related neck complaints: a randomized controlled trial

Increase in the prevalence of hypertension among adults exposed to the Great Chinese Famine during early life

Isolation and identification of Acanthamoeba strains from soil and tap water in Yanji, China

Enterococcus hirae biofilm formation on hospital material surfaces and effect of new biocides