The PFAS Health Study Systematic Literature Review Martyn Kirk, Kayla Smurthwaite, Jennifer Bräunig, Susan Trevenar, Cate D’Este, Robyn Lucas, Aparna Lal, Rosemary Korda, Archie Clements, Jochen Mueller, Bruce Armstrong Acknowledgements This research is a project of the National Centre for Epidemiology and Population Health, Research School of Population Health, the Australian National University. This Systematic Literature Review was commissioned by the Australian Government Department of Health. The information and opinions contained in it do not necessarily reflect the views or policy of the Research School of Population Health or the Australian Government Department of Health. We thank Liz Walker and Dagmar Ceramidas for their assistance in editing the systematic review and Kefyalew Addis Alene, Andrea Parisi, Claudia Sliming and Patiyan Andersson for their assistance in performing the reviews. SUGGESTED CITATION Kirk M,1 Smurthwaite K,1 Bräunig J,5 Trevenar S,1 D’Este C,1 Lucas R,1 Lal A,1 Korda R,1 Clements A,2 Mueller J,5 Armstrong B.3,4 The PFAS Health Study: Systematic Literature Review. Canberra: The Australian National University. 2018. 1. National Centre for Epidemiology and Population Health, Research School of Population Health, The Australian National University, Canberra, ACT, Australia 2. Research School of Population Health, The Australian National University, Canberra, ACT, Australia 3. Sydney School of Public Health, The University of Sydney, NSW, Australia 4. Sax Institute, Sydney, NSW, Australia 5. Queensland Alliance for Environmental Health Sciences, The University of Queensland Prof Martyn Kirk National Centre for Epidemiology and Population Health Research School of Population Health The Australian National University Acton ACT 2600 Australia T: 61 2 6125 5609 F: 61 2 6125 0740 E: [email protected] W: http://nceph.anu.edu.au/ Page | 2 Contents Acknowledgements ............................................................................................................... 2 Contents ............................................................................................................................... 3 Abbreviations ........................................................................................................................ 6 Plain Language Summary ................................................................................................... 11 Executive Summary ............................................................................................................ 12 Background ..................................................................................................................... 12 Key findings ..................................................................................................................... 12 Introduction ......................................................................................................................... 14 Key studies on human health .......................................................................................... 15 Previous systematic reviews ............................................................................................ 17 The present study ............................................................................................................ 18 Methods .............................................................................................................................. 19 Research question........................................................................................................... 19 Search strategy ............................................................................................................... 19 Inclusion & exclusion criteria ........................................................................................... 21 Data collection and screening .......................................................................................... 21 Hand-searching of included literature .............................................................................. 22 Quality assessment ......................................................................................................... 22 Meta-analysis .................................................................................................................. 23 Key findings ........................................................................................................................ 25 Identification of studies .................................................................................................... 25 Overview of studies ......................................................................................................... 25 Key health outcomes associated with PFAS .................................................................... 26 Neonatal, infant and maternal outcomes ............................................................................. 27 Measurements at birth ..................................................................................................... 27 Delivery outcomes ........................................................................................................... 40 Miscarriage ...................................................................................................................... 42 Stillbirth ........................................................................................................................... 42 Pregnancy loss (unspecified) ........................................................................................... 43 Mode of delivery .............................................................................................................. 43 Delivery complications ..................................................................................................... 43 Gender outcomes ............................................................................................................ 43 Maternal outcomes .......................................................................................................... 45 Page | 3 Neonatal and infant diagnoses ........................................................................................ 47 Growth during infancy ...................................................................................................... 49 Reproductive outcomes ...................................................................................................... 50 Reproductive hormone levels .......................................................................................... 50 Time to pregnancy (TTP), fecundity and infertility ............................................................ 60 Sperm characteristics ...................................................................................................... 65 Menstruation and menopause ......................................................................................... 68 Onset of puberty .............................................................................................................. 70 Congenital cryptorchidism and hypospadias .................................................................... 71 Metabolic effects ................................................................................................................. 72 Cholesterol and triglycerides ........................................................................................... 72 Kidney function ................................................................................................................ 80 Liver function ................................................................................................................... 82 Other metabolic outcomes ............................................................................................... 84 Thyroid outcomes ............................................................................................................... 86 Thyroid Stimulating Hormone (TSH) level ........................................................................ 86 Thyroxine (T4) level ......................................................................................................... 91 Triiodothyronine (T3) level ................................................................................................ 96 Thyroid disease ............................................................................................................. 101 Thyroglobulin levels ....................................................................................................... 102 Neurodevelopmental and neurophysiological outcomes .................................................... 103 Neurodevelopmental outcomes ..................................................................................... 103 Neurophysiological outcomes ........................................................................................ 108 Cancers ............................................................................................................................ 110 Diabetes............................................................................................................................ 115 Cardiovascular effects ....................................................................................................... 117 Overweight and obesity ..................................................................................................... 119 Immunological