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The association between maternal perfluoroalkyl substances exposure and early attention deficit hyperactivity disorder in children: a systematic review and meta-analysis

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Abstract

Some studies have shown that maternal exposure to perfluoroalkyl substances (PFASs) may be associated with early attention deficit hyperactivity disorder (ADHD) in children. The purpose of this systematic review and meta-analysis is to verify this association by reviewing existing studies and to provide a strong basis for preventing ADHD. The researchers searched electronic databases such as PubMed, Science Direct, Scopus, Google Scholar, Web of Science, and Embase for all studies published before October 2020. Finally, we included nine articles for analysis. Our meta-analysis showed that maternal exposure to PFASs was not significantly associated with the prevalence rate of early childhood ADHD (perfluorooctanoic acid (PFOA), odds ratio (OR) = 1.00, 95% confidence interval (95% CI) = 0.75–1.25; perfluorooctane sulfonate (PFOS), OR = 1.01, 95% CI = 0.88–1.14; perfluorohexane sulfonate (PFHxS), OR = 1.08, 95% CI = 0.80–1.09; perfluorononanoic acid (PFNA), OR = 1.13, 95% CI = 0.99–1.28; perfluorodecanoic acid (PFDA), OR = 1.23, 95% CI = 0.15–2.32). Due to significant heterogeneity, we subsequently performed subgroup analysis and sensitivity analysis. Through subgroup analysis, we found that PFOS concentration of children’s blood and the prevalence rate of early childhood ADHD were statistically positively correlated, and there was also a positive correlation between PFOS exposure and the prevalence rate of early childhood ADHD in the America. Moreover, there was also a statistically positive correlation between PFNA concentration in maternal blood and the prevalence rate of early childhood ADHD. Sensitivity analysis showed that the final results did not change much, the sensitivity was low, and the results were relatively stable. In conclusion, a causal relationship between maternal PFASs exposure and ADHD in children was unlikely. Among them, PFOS, PFNA, and ADHD might have positive associations worthy of further investigation.

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References

  • Antignac J-P, Veyrand B, Kadar H, Marchand P, Oleko A, Le Bizec B, Vandentorren S (2013) Occurrence of perfluorinated alkylated substances in breast milk of French women and relation with socio-demographical and clinical parameters: results of the ELFE pilot study. Chemosphere 91(6):802–808

    Article  CAS  Google Scholar 

  • Banerjee TD, Middleton F, Faraone SV (2007) Environmental risk factors for attention-deficit hyperactivity disorder. Acta Paediatr 96(9):1269–1274

    Article  Google Scholar 

  • Boas M, Feldt-Rasmussen U, Main KM (2012) Thyroid effects of endocrine disrupting chemicals. Mol Cell Endocrinol 355(2):240–248. https://doi.org/10.1016/j.mce.2011.09.005

    Article  CAS  Google Scholar 

  • Boronow KE, Brody JG, Schaider LA, Peaslee GF, Havas L, Cohn BA (2019) Serum concentrations of PFASs and exposure-related behaviors in African American and non-Hispanic white women. J Expo Sci Environ Epidemiol 29(2):206–217. https://doi.org/10.1038/s41370-018-0109-y

    Article  CAS  Google Scholar 

  • Butenhoff JL, Olsen GW, Pfahles-Hutchens A (2006) The applicability of biomonitoring data for perfluorooctanesulfonate to the environmental public health continuum. Environ Health Perspect 114(11):1776–1782

    Article  CAS  Google Scholar 

  • Chen M-H, Ha E-H, Liao H-F, Jeng S-F, Su Y-N, Wen T-W, Lien G-W, Chen C-Y, Hsieh W-S, Chen P-C (2013) Perfluorinated compound levels in cord blood and neurodevelopment at 2 years of age. Epidemiology:800–808

  • Comings DE, Chen TJH, Blum K, Mengucci JF, Meshkin B (2005) Neurogenetic interactions and aberrant behavioral co-morbidity of attention deficit hyperactivity disorder (ADHD): dispelling myths. Theor Biol Med Model 2(1):50

    Article  Google Scholar 

  • Dalahmeh S, Tirgani S, Komakech AJ, Niwagaba CB, Ahrens L (2018) Per- and polyfluoroalkyl substances (PFASs) in water, soil and plants in wetlands and agricultural areas in Kampala, Uganda. Sci Total Environ 631-632:660–667. https://doi.org/10.1016/j.scitotenv.2018.03.024

    Article  CAS  Google Scholar 

  • Fei C, Olsen J (2011) Prenatal exposure to perfluorinated chemicals and behavioral or coordination problems at age 7 years. Environ Health Perspect 119(4):573–578. https://doi.org/10.1289/ehp.1002026

    Article  CAS  Google Scholar 

  • Fei C, McLaughlin JK, Lipworth L, Olsen J (2008) Prenatal exposure to perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) and maternally reported developmental milestones in infancy. Environ Health Perspect 116(10):1391–1395. https://doi.org/10.1289/ehp.11277

    Article  CAS  Google Scholar 

  • Fernandez-Jaen A, Fernández-Mayoralas DM, Calleja-Perez B, Munoz-Jareno N, Lopez-Arribas S (2012) Genomic endophenotypes of attention deficit hyperactivity disorder. Rev Neurol 54(3):S81–S87

    Google Scholar 

  • Gaballah S, Swank A, Sobus JR, Howey XM, Schmid J, Catron T, McCord J, Hines E, Strynar M, Tal T (2020) Evaluation of developmental toxicity, developmental neurotoxicity, and tissue dose in zebrafish exposed to GenX and other PFAS. Environ Health Perspect 128(4):47005. https://doi.org/10.1289/ehp5843

    Article  CAS  Google Scholar 

  • Ghisi R, Vamerali T, Manzetti S (2019) Accumulation of perfluorinated alkyl substances (PFAS) in agricultural plants: a review. Environ Res 169:326–341. https://doi.org/10.1016/j.envres.2018.10.023

    Article  CAS  Google Scholar 

  • Guo XX, He QZ, Li W, Long DX, Pan XY, Chen C, Zeng HC (2017) Brain-derived neurotrophic factor mediated perfluorooctane sulfonate induced-neurotoxicity via epigenetics regulation in SK-N-SH Cells. Int J Mol Sci 18(4). https://doi.org/10.3390/ijms18040893

  • Harrad, S. and N. Wemken (2019). "Perfluoroalkyl substances in drinking water, indoor air and dust from Ireland: implications for human exposure." 53(22): 13449-13457.https://doi.org/10.1021/acs.est.9b04604

  • Hoffman K, Webster TF, Weisskopf MG, Weinberg J, Vieira VM (2010) Exposure to polyfluoroalkyl chemicals and attention deficit/hyperactivity disorder in US children 12–15 years of age. Environ Health Perspect 118(12):1762–1767

    Article  CAS  Google Scholar 

  • Hoyer BB, Ramlau-Hansen CH, Obel C, Pedersen HS, Hernik A, Ogniev V, Joensson BAG, Lindh CH, Rylander L, Rignell-Hydbom A, Bonde JP, Toft G (2015) Pregnancy serum concentrations of perfluorinated alkyl substances and offspring behaviour and motor development at age 5-9 years - a prospective study. Environ Health 14. https://doi.org/10.1186/1476-069x-14-2

  • Hoyer BB, Bonde JP, Tottenborg SS, Ramlau-Hansen CH, Lindh C, Pedersen HS, Toft G (2018) Exposure to perfluoroalkyl substances during pregnancy and child behaviour at 5 to 9 years of age. Horm Behav 101:105–112. https://doi.org/10.1016/j.yhbeh.2017.11.007

    Article  CAS  Google Scholar 

  • Ingelido AM, Abballe A, Gemma S, Dellatte E, Iacovella N, De Angelis G, Marra V, Russo F, Vazzoler M, Testai E, De Felip E (2020) Serum concentrations of perfluorinated alkyl substances in farmers living in areas affected by water contamination in the Veneto Region (Northern Italy). Environ Int 136:105435. https://doi.org/10.1016/j.envint.2019.105435

    Article  CAS  Google Scholar 

  • Kantiani L, Llorca M, Sanchís J, Farré M, Barceló D (2010) Emerging food contaminants: a review. Anal Bioanal Chem 398(6):2413–2427

    Article  CAS  Google Scholar 

  • Kishi R, Nakajima T, Goudarzi H, Kobayashi S, Sasaki S, Okada E, Miyashita C, Itoh S, Araki A, Ikeno T, Iwasaki Y, Nakazawa H (2015) 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 123(10):1038–1045. https://doi.org/10.1289/ehp.1408834

    Article  CAS  Google Scholar 

  • Knudsen A-KS, Long M, Pedersen HS, Bonefeld-Jørgensen EC (2018) Persistent organic pollutants and haematological markers in Greenlandic pregnant women: the ACCEPT sub-study. International journal of circumpolar health 77(1):1456303

    Article  Google Scholar 

  • Lenters V, Iszatt N, Forns J, Cechova E, Kocan A, Legler J, Leonards P, Stigum H, Eggesbo M (2019) Early-life exposure to persistent organic pollutants (OCPs, PBDEs, PCBs, PFASs) and attention-deficit/hyperactivity disorder: a multi-pollutant analysis of a Norwegian birth cohort. Environ Int 125:33–42. https://doi.org/10.1016/j.envint.2019.01.020

    Article  CAS  Google Scholar 

  • Li Z, Liu Q, Liu C, Li C, Li Y, Li S, Liu X, Shao J (2017) Evaluation of PFOS-mediated neurotoxicity in rat primary neurons and astrocytes cultured separately or in co-culture. Toxicol in Vitro 38:77–90. https://doi.org/10.1016/j.tiv.2016.11.002

    Article  CAS  Google Scholar 

  • Lien GW, Huang CC, Shiu JS, Chen MH, Hsieh WS, Guo YL, Chen PC (2016) Perfluoroalkyl substances in cord blood and attention deficit/hyperactivity disorder symptoms in seven-year-old children. Chemosphere 156:118–127. https://doi.org/10.1016/j.chemosphere.2016.04.102

    Article  CAS  Google Scholar 

  • Liew Z, Ritz B, von Ehrenstein OS, Bech BH, Nohr EA, Fei C, Bossi R, Henriksen TB, Bonefeld-Jorgensen EC, Olsen J (2015) Attention deficit/hyperactivity disorder and childhood autism in association with prenatal exposure to perfluoroalkyl substances: a nested case-control study in the Danish National Birth Cohort. Environ Health Perspect 123(4):367–373. https://doi.org/10.1289/ehp.1408412

    Article  Google Scholar 

  • Liu X, Qu A, Hu F, Yang Y, Cao Y (2017) Oxidative Damage on kidney of mice induced by PFOS-K. Progress in Modern Biomedicine 17(20):3842–3845+3859 (in chinese)

    Google Scholar 

  • Long Y, Wang Y, Ji G, Yan L, Hu F, Gu A (2013) Neurotoxicity of perfluorooctane sulfonate to hippocampal cells in adult mice. PLoS One 8(1):e54176. https://doi.org/10.1371/journal.pone.0054176

    Article  CAS  Google Scholar 

  • Martin MT, Brennan RJ, Hu W, Ayanoglu E, Lau C, Ren H, Wood CR, Corton JC, Kavlock RJ, Dix DJ (2007) Toxicogenomic study of triazole fungicides and perfluoroalkyl acids in rat livers predicts toxicity and categorizes chemicals based on mechanisms of toxicity. Toxicol Sci 97(2):595–613. https://doi.org/10.1093/toxsci/kfm065

    Article  CAS  Google Scholar 

  • Mohr JC, Steinhausen HC (2015) Time trends in incidence rates of diagnosed attention-deficit/hyperactivity disorder across 16 years in a nationwide Danish registry study. 76(3):e334–e341

  • Ode A, Källén K, Gustafsson P, Rylander L, Jönsson BA, Olofsson P, Ivarsson SA, Lindh CH, Rignell-Hydbom A (2014) Fetal exposure to perfluorinated compounds and attention deficit hyperactivity disorder in childhood. PLoS One 9(4):e95891

    Article  Google Scholar 

  • Oulhote Y, Steuerwald U, Debes F, Weihe P, Grandjean P (2016) Behavioral difficulties in 7-year old children in relation to developmental exposure to perfluorinated alkyl substances. Environ Int 97:237–245. https://doi.org/10.1016/j.envint.2016.09.015

    Article  CAS  Google Scholar 

  • Pennings JL, Jennen DG, Nygaard UC, Namork E, Haug LS, van Loveren H, Granum B (2016) Cord blood gene expression supports that prenatal exposure to perfluoroalkyl substances causes depressed immune functionality in early childhood. J Immunotoxicol 13(2):173–180. https://doi.org/10.3109/1547691x.2015.1029147

    Article  CAS  Google Scholar 

  • Quaak I, de Cock M, de Boer M, Lamoree M, Leonards P, van de Bor M (2016) Prenatal exposure to perfluoroalkyl substances and behavioral development in children. Int J Environ Res Public Health 13(5). https://doi.org/10.3390/ijerph13050511

  • Sheng N, Pan Y, Dai J (2018) Current research status of several emerging per- and polyfluoroalkyl substances (PFASs). Journal of Anhui University (Natural Science Edition) 42(06):3–13 (in chinese)

    Google Scholar 

  • Shigei M, Ahrens L, Hazaymeh A, Dalahmeh SS (2020) Per- and polyfluoroalkyl substances in water and soil in wastewater-irrigated farmland in Jordan. Sci Total Environ 716:137057. https://doi.org/10.1016/j.scitotenv.2020.137057

    Article  CAS  Google Scholar 

  • Stein CR, Savitz DA (2011) Serum perfluorinated compound concentration and attention deficit/hyperactivity disorder in children 5-18 years of age. Environ Health Perspect 119(10):1466–1471. https://doi.org/10.1289/ehp.1003538

    Article  CAS  Google Scholar 

  • Stein CR, Savitz DA, Bellinger DC (2013) Perfluorooctanoate and neuropsychological outcomes in children. Epidemiology 24(4):590–599. https://doi.org/10.1097/EDE.0b013e3182944432

    Article  Google Scholar 

  • Stein CR, Savitz DA, Bellinger DC (2014) Perfluorooctanoate exposure in a highly exposed community and parent and teacher reports of behaviour in 6-12-year-old children. Paediatr Perinat Epidemiol 28(2):146–156. https://doi.org/10.1111/ppe.12097

    Article  Google Scholar 

  • Stratakis N, V CDR, Jin KM, Valvi D, Siskos AP, Maitre L, Garcia E, Varo N, Zhao Y, Roumeliotaki T, Vafeiadi M, Urquiza J, Fernández-Barrés S, Heude B, Basagana X, Casas M, Fossati S, Gražulevičienė R, Andrušaitytė S, Uppal K, McEachan RRC, Papadopoulou E, Robinson O, Haug LS, Wright J, Vos MB, Keun HC, Vrijheid M, Berhane KT, McConnell R, Chatzi L (2020) Prenatal exposure to perfluoroalkyl substances associated with increased susceptibility to liver injury in children. Hepatology 72(5):1758–1770. https://doi.org/10.1002/hep.31483

    Article  CAS  Google Scholar 

  • Strom M, Hansen S, Olsen SF, Haug LS, Rantakokko P, Kiviranta H, Halldorsson TI (2014) Persistent organic pollutants measured in maternal serum and offspring neurodevelopmental outcomes--a prospective study with long-term follow-up. Environ Int 68:41–48. https://doi.org/10.1016/j.envint.2014.03.002

    Article  CAS  Google Scholar 

  • Sznajder-Katarzyńska K, Surma M, Cieślik E, Wiczkowski W (2018) The perfluoroalkyl substances (PFASs) contamination of fruits and vegetables. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 35(9):1776–1786. https://doi.org/10.1080/19440049.2018.1502477

    Article  CAS  Google Scholar 

  • Wang Y, Zhao H, Zhang Q, Liu W, Quan X (2015) Perfluorooctane sulfonate induces apoptosis of hippocampal neurons in rat offspring associated with calcium overload. Toxicology Research 4(4):931–938. https://doi.org/10.1039/C4TX00177J

    Article  CAS  Google Scholar 

  • Wang H, Du H, Yang J, Jiang H, O K, Xu L, Liu S, Yi J, Qian X, Chen Y, Jiang Q, He G (2019a) PFOS, PFOA, estrogen homeostasis, and birth size in Chinese infants. Chemosphere 221:349–355. https://doi.org/10.1016/j.chemosphere.2019.01.061

    Article  CAS  Google Scholar 

  • Wang J, Zeng XW, Bloom MS, Qian Z, Hinyard LJ, Belue R, Lin S, Wang SQ, Tian YP, Yang M, Chu C, Gurram N, Hu LW, Liu KK, Yang BY, Feng D, Liu RQ, Dong GH (2019b) Renal function and isomers of perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS): isomers of C8 Health Project in China. Chemosphere 218:1042–1049. https://doi.org/10.1016/j.chemosphere.2018.11.191

    Article  CAS  Google Scholar 

  • Wang Y, Wang L, Chang W, Zhang Y, Zhang Y, Liu W (2019c) Neurotoxic effects of perfluoroalkyl acids: neurobehavioral deficit and its molecular mechanism. Toxicol Lett 305:65–72. https://doi.org/10.1016/j.toxlet.2019.01.012

    Article  CAS  Google Scholar 

  • Yu WG, Liu W, Jin YH, Liu XH, Wang FQ, Liu L, Nakayama SF (2009) Prenatal and postnatal impact of perfluorooctane sulfonate (PFOS) on rat development: a cross-foster study on chemical burden and thyroid hormone system. Environ Sci Technol 43(21):8416–8422. https://doi.org/10.1021/es901602d

    Article  CAS  Google Scholar 

  • Zafeiraki E, Vassiliadou I, Costopoulou D, Leondiadis L, Schafft HA, Hoogenboom RL, van Leeuwen SP (2016) Perfluoroalkylated substances in edible livers of farm animals, including depuration behaviour in young sheep fed with contaminated grass. Chemosphere 156:280–285

    Article  CAS  Google Scholar 

  • Zhang W, Liu X, Gu Q, Liao R, Ran L (2007) An epidemiological investigation of ADHD in six cities. Chinese Journal of Clinical Psychology (1):23–25 (in chinese)

  • Zhang YZ, Wang B, Wang W, Li WC, Huang J, Deng SB, Wang YJ, Yu G (2016) Occurrence and source apportionment of per- and poly-fluorinated compounds (PFCs) in North Canal Basin, Beijing. Sci Rep 6:36683. https://doi.org/10.1038/srep36683

    Article  CAS  Google Scholar 

  • Zhou Y, Shen J, Mao Y, Jin F (2018) Research progress of the relationship between perfluoroalkyl and polyfluoroalkyl substances and human reproduction. Chinese J Reprod Cont 11:14 (in chinese)

    Google Scholar 

  • Zhou X, Liu Z, Meng X, Wang Y, Long J, Zhao W (2019) Research progress on immunotoxicities induced by perfluorooctanoic acid. J Environ Occup Med 36(03):266–271 (in chinese)

    Google Scholar 

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Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Funding

This research was supported by the Health Department Science Research Foundation of Hebei Province (Project No.20090057) and Innovative experiment project of Hebei Medical University (NO.USIP2020164).

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Conceived and designed the experiments, XLZ, XHL, and SJS; performed the experiments, ZXL, WJW, RL, XW, and YXN; analyzed the data, ABQ and TRC; contributed analysis tools, XLZ; wrote the paper, XHL, ABQ, and TRC. All authors read and approved the final manuscript.

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Correspondence to Xuehui Liu or Xiaolin Zhang.

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Qu, A., Cao, T., Li, Z. et al. The association between maternal perfluoroalkyl substances exposure and early attention deficit hyperactivity disorder in children: a systematic review and meta-analysis. Environ Sci Pollut Res 28, 67066–67081 (2021). https://doi.org/10.1007/s11356-021-15136-2

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